Genomes and Genes
Gene Symbol: Polr2a
Description: polymerase (RNA) II (DNA directed) polypeptide A
Alias: 220kDa, Rpb1, Rpo2-1, DNA-directed RNA polymerase II subunit RPB1, DNA-directed RNA polymerase II subunit A, DNA-directed RNA polymerase III largest subunit, RNA polymerase II 1, RNA polymerase II subunit B1
- Dankort D, Filenova E, Collado M, Serrano M, Jones K, McMahon M. A new mouse model to explore the initiation, progression, and therapy of BRAFV600E-induced lung tumors. Genes Dev. 2007;21:379-84 pubmed..Consistent with Ink4a/Arf and TP53 tumor suppressor function, BRaf(VE) expression combined with mutation of either locus led to cancer progression. ..
- Barrera L, Li Z, Smith A, Arden K, Cavenee W, Zhang M, et al. Genome-wide mapping and analysis of active promoters in mouse embryonic stem cells and adult organs. Genome Res. 2008;18:46-59 pubmedBy integrating genome-wide maps of RNA polymerase II (Polr2a) binding with gene expression data and H3ac and H3K4me3 profiles, we characterized promoters with enriched activity in mouse embryonic stem cells (mES) as well as adult brain, ..
- Montano M, Doughman Y, Deng H, Chaplin L, Yang J, Wang N, et al. Mutation of the HEXIM1 gene results in defects during heart and vascular development partly through downregulation of vascular endothelial growth factor. Circ Res. 2008;102:415-22 pubmed..The basis for this role of HEXIM1 is that VEGF is a direct transcriptional target of HEXIM1, and involves attenuation a repressive effects of C/EBPalpha on VEGF gene transcription. ..
- Jimenez Guri E, Udina F, Colas J, Sharpe J, Padron Barthe L, Torres M, et al. Clonal analysis in mice underlines the importance of rhombomeric boundaries in cell movement restriction during hindbrain segmentation. PLoS ONE. 2010;5:e10112 pubmed publisher..We show that the rhombomeric boundaries themselves are involved in cell movement restriction, although an underlying pre-pattern during early embryonic development might influence the way that cell populations organize. ..
- Lacroix M, Caramel J, Goguet Rubio P, Linares L, Estrach S, Hatchi E, et al. Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis. Proc Natl Acad Sci U S A. 2010;107:21076-81 pubmed publisher..Our data identify a regulatory axis essential for ESC-dependent skin homeostasis implicating E4F1 and the Bmi1-Arf-p53 pathway. ..
- Mijimolle N, Velasco J, Dubus P, Guerra C, Weinbaum C, Casey P, et al. Protein farnesyltransferase in embryogenesis, adult homeostasis, and tumor development. Cancer Cell. 2005;7:313-24 pubmed..However, elimination of FTase during tumor progression had a limited but significant inhibitory effect. These results should help to better understand the role of protein farnesylation in normal tissues and in tumor development. ..
- Guerra C, Mijimolle N, Dhawahir A, Dubus P, Barradas M, Serrano M, et al. Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context. Cancer Cell. 2003;4:111-20 pubmed..These results indicate that neoplastic growth induced by an endogenous K-ras oncogene depends upon cellular context. ..
- Manchado E, Guillamot M, de Carcer G, Eguren M, Trickey M, Garcia Higuera I, et al. Targeting mitotic exit leads to tumor regression in vivo: Modulation by Cdk1, Mastl, and the PP2A/B55?,? phosphatase. Cancer Cell. 2010;18:641-54 pubmed publisher..These data illustrate the relevance of critical players of mitotic exit in mammals and their implications in the balance between cell death and mitotic exit in tumor cells. ..
- Navas C, Hernández Porras I, Schuhmacher A, Sibilia M, Guerra C, Barbacid M. EGF receptor signaling is essential for k-ras oncogene-driven pancreatic ductal adenocarcinoma. Cancer Cell. 2012;22:318-30 pubmed publisher..These findings may provide the bases for more rational approaches to treat pancreatic tumors in the clinic. ..
- Acker J, Mattei M, Wintzerith M, Roeckel N, Depetris D, Vigneron M, et al. Chromosomal localization of human RNA polymerase II subunit genes. Genomics. 1994;20:496-9 pubmed..3, and 19q12, respectively). Thus, if assembly of active polymerase molecules requires coordinated expression from these independent genes, mechanisms that ensure tight coregulation of the corresponding promoters must exist. ..
- Yasukawa T, Kamura T, Kitajima S, Conaway R, Conaway J, Aso T. Mammalian Elongin A complex mediates DNA-damage-induced ubiquitylation and degradation of Rpb1. EMBO J. 2008;27:3256-66 pubmed publisher..Here, we have shown that both the ubiquitylation and proteasomal degradation of the largest subunit of pol II (Rpb1) following UV-irradiation are significantly suppressed in Elongin A-deficient cells; however, in both cases ..
- Yakovchuk P, Goodrich J, Kugel J. B2 RNA and Alu RNA repress transcription by disrupting contacts between RNA polymerase II and promoter DNA within assembled complexes. Proc Natl Acad Sci U S A. 2009;106:5569-74 pubmed publisher..In the absence of its normal contacts with the promoter, Pol II is likely held in these inactive complexes on DNA through interactions with promoter-bound TATA box-binding protein and transcription factor IIB. ..
- Ji X, Zhou Y, Pandit S, Huang J, Li H, Lin C, et al. SR proteins collaborate with 7SK and promoter-associated nascent RNA to release paused polymerase. Cell. 2013;153:855-68 pubmed publisher..These findings reveal an unanticipated SR protein function, a role for promoter-proximal nascent RNA in gene activation, and an analogous mechanism to HIV Tat/TAR for activating cellular genes. ..
- Zhao L, Ba X, Wang X, Zhu X, Wang L, Zeng X. BAF complex is closely related to and interacts with NF1/CTF and RNA polymerase II in gene transcriptional activation. Acta Biochim Biophys Sin (Shanghai). 2005;37:440-6 pubmed..The combined results suggested that BAF complexes can interact with NF1/CTF and RNAP II, and this interaction is closely dependent on the activation of gene transcription. ..
- O GORMAN S, Dagenais N, Qian M, Marchuk Y. Protamine-Cre recombinase transgenes efficiently recombine target sequences in the male germ line of mice, but not in embryonic stem cells. Proc Natl Acad Sci U S A. 1997;94:14602-7 pubmed
- Yurttas P, Vitale A, Fitzhenry R, Cohen Gould L, Wu W, Gossen J, et al. Role for PADI6 and the cytoplasmic lattices in ribosomal storage in oocytes and translational control in the early mouse embryo. Development. 2008;135:2627-36 pubmed publisher..These results suggest that, in mammals, ribosomal components are stored in the oocyte CPLs and are required for protein translation during early development. ..
- Kalcheva I, Plass C, Sait S, Eddy R, Shows T, Watkins Chow D, et al. Comparative mapping of the imprinted U2afbpL gene on mouse chromosome 11 and human chromosome 5. Cytogenet Cell Genet. 1995;68:19-24 pubmed..The location of the human homologue has been determined using both somatic cell hybrid genetic analysis and fluorescence in situ hybridization. These analyses have mapped the human locus U2AFBPL to human chromosome 5q23-->q31. ..
- Barrière C, Santamaria D, Cerqueira A, Galan J, Martin A, Ortega S, et al. Mice thrive without Cdk4 and Cdk2. Mol Oncol. 2007;1:72-83 pubmed publisher..These observations indicate that Cdk4 and Cdk2 are dispensable for the mammalian cell cycle and for adult homeostasis. ..
- Kraemer N, Neubert G, Issa L, Ninnemann O, Seiler A, Kaindl A. Reference genes in the developing murine brain and in differentiating embryonic stem cells. Neurol Res. 2012;34:664-8 pubmed publisher..Based on our results, we suggest for gene expression analysis in the context of neurodevelopment the usage of RpII as a reference gene for mESC and Gapdh or Hprt for the murine neocortex. ..
- Emili A, Shales M, McCracken S, Xie W, Tucker P, Kobayashi R, et al. Splicing and transcription-associated proteins PSF and p54nrb/nonO bind to the RNA polymerase II CTD. RNA. 2002;8:1102-11 pubmed..PSF and p54nrb/NonO may therefore provide a direct physical link between the pol II CTD and pre-mRNA processing components, at both the initiation and elongation phases of transcription. ..
- Ding L, Paszkowski Rogacz M, Nitzsche A, Slabicki M, Heninger A, de Vries I, et al. A genome-scale RNAi screen for Oct4 modulators defines a role of the Paf1 complex for embryonic stem cell identity. Cell Stem Cell. 2009;4:403-15 pubmed publisher..We propose that the Paf1C plays an important role in maintaining ESC identity. ..
- Pavri R, Lewis B, Kim T, Dilworth F, Erdjument Bromage H, Tempst P, et al. PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator. Mol Cell. 2005;18:83-96 pubmed..PARP-1 appears to function as a specificity factor regulating the RA-induced switch of Mediator from the inactive (Cdk8+) to the active (Cdk8-) state in RAR-dependent transcription. ..
- Brookes E, de Santiago I, Hebenstreit D, Morris K, Carroll T, Xie S, et al. Polycomb associates genome-wide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs. Cell Stem Cell. 2012;10:157-70 pubmed publisher..We show that this group of PRC targets switches between active and PRC-repressed states within the ESC population, and that many have roles in metabolism. ..
- GalvÃ£o Ferreira P, Lipinski M, Santos F, Barco A, Costa R. Skill Learning Modulates RNA Pol II Poising at Immediate Early Genes in the Adult Striatum. Eneuro. 2017;4: pubmed publisher..Pol II paused at promoter-proximal regions, characterized by a Ser5P+-rich and Ser2P+-poor RPB1 CTD) to active elongation, has emerged as a major step in transcriptional regulation across several organisms, ..
- Corden J, Cadena D, Ahearn J, Dahmus M. A unique structure at the carboxyl terminus of the largest subunit of eukaryotic RNA polymerase II. Proc Natl Acad Sci U S A. 1985;82:7934-8 pubmed..This sequence is also unusual in that it contains a high percentage of potential phosphorylation sites. ..
- Gee J, Smith N, Fernandez F, Economo M, Brunert D, Rothermel M, et al. Imaging activity in neurons and glia with a Polr2a-based and cre-dependent GCaMP5G-IRES-tdTomato reporter mouse. Neuron. 2014;83:1058-72 pubmed publisher..Instead of targeting the ROSA26 locus, we inserted the reporter cassette nearby the ubiquitously expressed Polr2a gene without disrupting locus integrity...
- Drori A, Messerle M, Brune W, Tirosh B. Lack of XBP-1 impedes murine cytomegalovirus gene expression. PLoS ONE. 2014;9:e110942 pubmed publisher..Our data indicate that removal of XBP-1 confers a kinetic delay in early stages of MCMV infection and suggest that the late targeting of IRE1 is aimed at inhibiting activities other than the splicing of XBP-1 mRNA. ..
- Hoffmeyer K, Raggioli A, Rudloff S, Anton R, Hierholzer A, Del Valle I, et al. Wnt/?-catenin signaling regulates telomerase in stem cells and cancer cells. Science. 2012;336:1549-54 pubmed publisher..We uncover a previously unknown link between the stem cell and oncogenic potential whereby ?-catenin regulates Tert expression, and thereby telomere length, which could be critical in human regenerative therapy and cancer. ..
- Sabbattini P, Sjoberg M, Nikic S, Frangini A, Holmqvist P, Kunowska N, et al. An H3K9/S10 methyl-phospho switch modulates Polycomb and Pol II binding at repressed genes during differentiation. Mol Biol Cell. 2014;25:904-15 pubmed publisher..Our results provide evidence of a novel developmentally regulated methyl-phospho switch that modulates Polycomb regulation in differentiated cells and stabilizes repressed states. ..
- Galatioto J, Mascareno E, Siddiqui M. CLP-1 associates with MyoD and HDAC to restore skeletal muscle cell regeneration. J Cell Sci. 2010;123:3789-95 pubmed publisher..These findings suggest a novel transcriptional paradigm whereby CLP-1, in conjunction with MyoD and HDAC, acts to inhibit growth-related gene expression, a requirement for myoblasts to exit the cell cycle and transit to myotubes. ..
- Vizlin Hodzic D, Johansson H, Ryme J, Simonsson T, Simonsson S. SAF-A has a role in transcriptional regulation of Oct4 in ES cells through promoter binding. Cell Reprogram. 2011;13:13-27 pubmed publisher..The number of endogenous SAF-A:Oct4 and SAF-A:Sox2 complexes decreases upon LIF depletion. These discoveries allow us to propose a model for activation of Oct4 transcription. ..
- Kabe Y, Yamada J, Uga H, Yamaguchi Y, Wada T, Handa H. NF-Y is essential for the recruitment of RNA polymerase II and inducible transcription of several CCAAT box-containing genes. Mol Cell Biol. 2005;25:512-22 pubmed
- Sanchez Aguilera A, Arranz L, Martin Perez D, García García A, Stavropoulou V, Kubovcakova L, et al. Estrogen signaling selectively induces apoptosis of hematopoietic progenitors and myeloid neoplasms without harming steady-state hematopoiesis. Cell Stem Cell. 2014;15:791-804 pubmed publisher..Together, these results uncover specific regulation of hematopoietic progenitors by estrogens and potential antileukemic properties of SERMs. ..
- Lorincz M, Dickerson D, Schmitt M, Groudine M. Intragenic DNA methylation alters chromatin structure and elongation efficiency in mammalian cells. Nat Struct Mol Biol. 2004;11:1068-75 pubmed..As the methylated region adopts a closed chromatin structure in vivo, we propose that dense intragenic DNA methylation in mammalian cells initiates formation of a chromatin structure that reduces the efficiency of Pol II elongation. ..
- Hatchi E, Rodier G, Lacroix M, Caramel J, Kirsh O, Jacquet C, et al. E4F1 deficiency results in oxidative stress-mediated cell death of leukemic cells. J Exp Med. 2011;208:1403-17 pubmed publisher..Together, these data reveal a role for E4F1 in the survival of myeloid leukemic cells and support the notion that targeting E4F1 activities might have therapeutic interest. ..
- Nechanitzky R, Akbas D, Scherer S, Gyory I, Hoyler T, Ramamoorthy S, et al. Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells. Nat Immunol. 2013;14:867-75 pubmed publisher..Thus, both EBF1 and Pax5 are required for B lineage commitment by repressing distinct and common determinants of alternative cell fates. ..
- Roselló Díez A, Arques C, Delgado I, Giovinazzo G, Torres M. Diffusible signals and epigenetic timing cooperate in late proximo-distal limb patterning. Development. 2014;141:1534-43 pubmed publisher..This model is compatible with the most recent genetic analyses and underscores the importance of growth during the time-dependent patterning phase, providing a new mechanistic framework for understanding congenital limb defects. ..
- Blasco R, Francoz S, Santamaria D, Canamero M, Dubus P, Charron J, et al. c-Raf, but not B-Raf, is essential for development of K-Ras oncogene-driven non-small cell lung carcinoma. Cancer Cell. 2011;19:652-63 pubmed publisher..These results indicate that c-Raf plays a unique role in mediating K-Ras signaling and makes it a suitable target for therapeutic intervention. ..
- Padmanabhan K, Robles M, Westerling T, Weitz C. Feedback regulation of transcriptional termination by the mammalian circadian clock PERIOD complex. Science. 2012;337:599-602 pubmed publisher..Circadian clock negative feedback thus includes direct control of transcriptional termination. ..
- Wintzerith M, Acker J, Vicaire S, Vigneron M, Kedinger C. Complete sequence of the human RNA polymerase II largest subunit. Nucleic Acids Res. 1992;20:910 pubmed
- Hsu L, Liu S, Abedinpour F, Beech R, Lahti J, Kidd V, et al. The murine G+C-rich promoter binding protein mGPBP is required for promoter-specific transcription. Mol Cell Biol. 2003;23:8773-85 pubmed
- Bartolomei M, Corden J. Localization of an alpha-amanitin resistance mutation in the gene encoding the largest subunit of mouse RNA polymerase II. Mol Cell Biol. 1987;7:586-94 pubmed..Knowledge of the position of the A21 mutation should facilitate the study of the mechanism of alpha-amanitin resistance. Furthermore, the A21 gene will be useful for studying the phenotype of site-directed mutations in the RPII215 gene. ..
- Chiang P, Baldacci P, Babinet C, Camper S, Watkins Chow D, Baker D, et al. Linkage mapping of murine homolog of the yeast SPT6 gene to MMU11B1. Mamm Genome. 1996;7:459-60 pubmed
- Hebert J, McConnell S. Targeting of cre to the Foxg1 (BF-1) locus mediates loxP recombination in the telencephalon and other developing head structures. Dev Biol. 2000;222:296-306 pubmed..Collectively, these data show that Foxg1-Cre mice should be useful in the deletion or ectopic expression of any floxed target gene in a Foxg1-like pattern. ..
- Yakovchuk P, Goodrich J, Kugel J. B2 RNA represses TFIIH phosphorylation of RNA polymerase II. Transcription. 2011;2:45-9 pubmed publisher..Biochemical assays revealed that B2 RNA, when present with Pol II in promoter-bound complexes, specifically represses CTD phosphorylation by TFIIH. ..
- Münke M, Francke U. The physical map of Mus musculus chromosome 11 reveals evolutionary relationships with different syntenic groups of genes in Homo sapiens. J Mol Evol. 1987;25:134-40 pubmed..The delineation of conserved chromosome regions has important implications for the understanding of karyotype evolution in mammalian species and for the development of animal models of human genetic diseases. ..
- Devaiah B, Lewis B, Cherman N, Hewitt M, Albrecht B, Robey P, et al. BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc Natl Acad Sci U S A. 2012;109:6927-32 pubmed publisher..Phosphorylation of the CTD Ser2 is inhibited in vivo by a BRD4 inhibitor that blocks its binding to chromatin. Our finding that BRD4 is an RNA polymerase II CTD Ser2 kinase implicates it as a regulator of eukaryotic transcription. ..
- Bigi A, Beltrami E, Trinei M, Stendardo M, Pelicci P, Giorgio M. Cyclophilin D counteracts P53-mediated growth arrest and promotes Ras tumorigenesis. Oncogene. 2016;35:5132-43 pubmed publisher..All together, these findings indicate that the countering effect of CypD on the p53-p21 pathway participates in oncogene-dependent transformation. ..
- Wang A, Zare H, Mousavi K, Wang C, Moravec C, Sirotkin H, et al. The histone chaperone Spt6 coordinates histone H3K27 demethylation and myogenesis. EMBO J. 2013;32:1075-86 pubmed publisher..Our data indicate that, through cooperation with PolII and KDM6A, Spt6 orchestrates removal of H3K27me3, thus controlling developmental gene expression and cell differentiation. ..
- Micucci C, Orciari S, Catalano A. Hyperglycemia promotes K-Ras-induced lung tumorigenesis through BASCs amplification. PLoS ONE. 2014;9:e105550 pubmed publisher..Our novel findings suggest that anti-hyperglycemic drugs, such as metformin, may act as therapeutic agent to restrict lung neoplasia promotion and progression. ..
- Drosten M, Dhawahir A, Sum E, Urosevic J, Lechuga C, Esteban L, et al. Genetic analysis of Ras signalling pathways in cell proliferation, migration and survival. EMBO J. 2010;29:1091-104 pubmed publisher..Rasless MEFs had normal levels of Cyclin D1/Cdk4 and Cyclin E/Cdk2. However, these complexes were inactive. Inactivation of the pocket proteins or knock down of pRb relieved MEFs from their dependence on Ras signalling to proliferate. ..
- Drosten M, Lechuga C, Barbacid M. Ras signaling is essential for skin development. Oncogene. 2014;33:2857-65 pubmed publisher..These observations provide genetic evidence for an essential role of Ras proteins in the control of keratinocyte and epidermal proliferation. ..
- Pravtcheva D, Rabin M, Bartolomei M, Corden J, Ruddle F. Chromosomal assignment of gene encoding the largest subunit of RNA polymerase II in the mouse. Somat Cell Mol Genet. 1986;12:523-8 pubmed..This assignment extends the previously defined homology between mouse chromosome 11 and human chromosome 17. ..
- Yoh S, Lucas J, Jones K. The Iws1:Spt6:CTD complex controls cotranscriptional mRNA biosynthesis and HYPB/Setd2-mediated histone H3K36 methylation. Genes Dev. 2008;22:3422-34 pubmed publisher..Thus Iws1 connects two distinct CTD-binding proteins, Spt6 and HYPB/Setd2, in a megacomplex that affects mRNA export as well as the histone modification state of active genes. ..
- Gyory I, Boller S, Nechanitzky R, Mandel E, Pott S, Liu E, et al. Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells. Genes Dev. 2012;26:668-82 pubmed publisher..By regulating important components of transcription factor and signaling networks, Ebf1 appears to be involved in the coordination of cell proliferation, survival, and differentiation at multiple stages of B lymphopoiesis. ..
- Hintermair C, Heidemann M, Koch F, Descostes N, Gut M, Gut I, et al. Threonine-4 of mammalian RNA polymerase II CTD is targeted by Polo-like kinase 3 and required for transcriptional elongation. EMBO J. 2012;31:2784-97 pubmed publisher..consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 at the carboxy-terminal domain (CTD) of the large subunit (Rpb1)...
- Bourquin J, Stagljar I, Meier P, Moosmann P, Silke J, Baechi T, et al. A serine/arginine-rich nuclear matrix cyclophilin interacts with the C-terminal domain of RNA polymerase II. Nucleic Acids Res. 1997;25:2055-61 pubmed
- Tanner S, Stagljar I, Georgiev O, Schaffner W, Bourquin J. A novel SR-related protein specifically interacts with the carboxy-terminal domain (CTD) of RNA polymerase II through a conserved interaction domain. Biol Chem. 1997;378:565-71 pubmed..The DNA fragment library of the SRrp129 clone was then used in the yeast two-hybrid system to identify the 100-amino acid domain that interacts with the CTD of RNA polymerase II. ..
- Morris Rosendahl D, Schriever Schwemmer G, Robinson T. Derivation and characterization of a somatic cell hybrid containing the portion of mouse chromosome 11 (MMU11) homologous to human chromosome 17q. J Hered. 1996;87:252-8 pubmed..Loci for D11Mit5, Rpo2-1, Trp53, Glut4, Acrb, and Atplb2 could all be localized proximal to the T16Ad breakpoint in band B5, between bands B1 and B5 on MMU11. ..
- Hernández Porras I, Schuhmacher A, Garcia Medina R, Jimenez B, Canamero M, de Martino A, et al. K-Ras(V14I) -induced Noonan syndrome predisposes to tumour development in mice. J Pathol. 2016;239:206-17 pubmed publisher..Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. ..
- Pontes Quero S, Heredia L, Casquero García V, Fernández Chacón M, Luo W, Hermoso A, et al. Dual ifgMosaic: A Versatile Method for Multispectral and Combinatorial Mosaic Gene-Function Analysis. Cell. 2017;170:800-814.e18 pubmed publisher..This technology enables the interrogation of multiple and combinatorial gene function with high temporal and cellular resolution. ..
- Tierling S, Dalbert S, Schoppenhorst S, Tsai C, Oliger S, Ferguson Smith A, et al. High-resolution map and imprinting analysis of the Gtl2-Dnchc1 domain on mouse chromosome 12. Genomics. 2006;87:225-35 pubmed..Hence, tissue-specific coregulation of maternally expressed genes might be an important feature of this domain. ..
- Seki Y, Yamaji M, Yabuta Y, Sano M, Shigeta M, Matsui Y, et al. Cellular dynamics associated with the genome-wide epigenetic reprogramming in migrating primordial germ cells in mice. Development. 2007;134:2627-38 pubmed..We suggest the possibility that active repression of an essential enzyme and subsequent unique cellular dynamics ensures successful implementation of genome-wide epigenetic reprogramming in migrating PGCs. ..
- Tufail Y, Cook D, Fourgeaud L, Powers C, Merten K, Clark C, et al. Phosphatidylserine Exposure Controls Viral Innate Immune Responses by Microglia. Neuron. 2017;93:574-586.e8 pubmed publisher..Our study identifies PLSCR1 as a potent target through which the innate immune response to viral vectors, and potentially other stimuli, may be controlled. ..
- Calés C, Román Trufero M, Pavón L, Serrano I, Melgar T, Endoh M, et al. Inactivation of the polycomb group protein Ring1B unveils an antiproliferative role in hematopoietic cell expansion and cooperation with tumorigenesis associated with Ink4a deletion. Mol Cell Biol. 2008;28:1018-28 pubmed..The novel antiproliferative role of Ring1B's downregulation of a cell cycle activator may play an important role in the tight control of hematopoietic cell turnover. ..
- Ivanovitch K, TemiÃ±o S, Torres M. Live imaging of heart tube development in mouse reveals alternating phases of cardiac differentiation and morphogenesis. elife. 2017;6: pubmed publisher..These results reveal tissue-level coordination between morphogenesis and differentiation during HT formation and provide a new framework to understand heart development. ..
- Blas Rus N, Bustos Morán E, Perez de Castro I, de Carcer G, Borroto A, Camafeita E, et al. Aurora A drives early signalling and vesicle dynamics during T-cell activation. Nat Commun. 2016;7:11389 pubmed publisher..These findings implicate Aurora A in the propagation of the TCR activation signal. ..
- Baltanás F, Perez Andres M, Ginel Picardo A, Diaz D, Jimeno D, Liceras Boillos P, et al. Functional redundancy of Sos1 and Sos2 for lymphopoiesis and organismal homeostasis and survival. Mol Cell Biol. 2013;33:4562-78 pubmed publisher..Our data demonstrate functional redundancy between Sos1 and Sos2 for homeostasis and survival of the full organism and for development and maturation of T and B lymphocytes. ..
- Spicer A, Roller M, Camper S, McPherson J, Wasmuth J, Hakim S, et al. The human and mouse receptors for hyaluronan-mediated motility, RHAMM, genes (HMMR) map to human chromosome 5q33.2-qter and mouse chromosome 11. Genomics. 1995;30:115-7 pubmed..The RHAMM gene location and its ability to transform cells when overexpressed implicate RHAMM as a possible candidate gene in the pathogenesis of the recently described t(5;14)(q33-q34;q11) acute lymphoblastic leukemias. ..
- Litingtung Y, Lawler A, Sebald S, Lee E, Gearhart J, Westphal H, et al. Growth retardation and neonatal lethality in mice with a homozygous deletion in the C-terminal domain of RNA polymerase II. Mol Gen Genet. 1999;261:100-5 pubmed..The gene targeting approach described here should be useful for making further deletions in the CTD and may be of general applicability where it is desirable to engineer specific mutations in the germline of mice. ..
- Ventura J, Tenbaum S, Perdiguero E, Huth M, Guerra C, Barbacid M, et al. p38alpha MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation. Nat Genet. 2007;39:750-8 pubmed..Our results indicate that by coordinating proliferation and differentiation signals in lung stem and progenitor cells, p38alpha has a key role in the regulation of lung cell renewal and tumorigenesis. ..
- Efeyan A, Murga M, Martinez Pastor B, Ortega Molina A, Soria R, Collado M, et al. Limited role of murine ATM in oncogene-induced senescence and p53-dependent tumor suppression. PLoS ONE. 2009;4:e5475 pubmed publisher..Regarding murine Atm, our data suggest that it plays a minor role in oncogene-induced senescence or in p53-dependent tumor suppression, being its tumor suppressive activity probably limited to the maintenance of genomic stability. ..
- Nimura K, Ura K, Shiratori H, Ikawa M, Okabe M, Schwartz R, et al. A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome. Nature. 2009;460:287-91 pubmed publisher..We propose that WHSC1 functions together with developmental transcription factors to prevent the inappropriate transcription that can lead to various pathophysiologies. ..
- Abe K, Inoue A, Suzuki M, Aoki F. Global gene silencing is caused by the dissociation of RNA polymerase II from DNA in mouse oocytes. J Reprod Dev. 2010;56:502-7 pubmed..Here, we investigated the involvement of RPB1, the largest subunit of RNA polymerase II (RNAP II), in the regulation of this transcriptional silencing mechanism...
- Puyol M, Martin A, Dubus P, Mulero F, Pizcueta P, Khan G, et al. A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma. Cancer Cell. 2010;18:63-73 pubmed publisher..These observations suggest that robust and selective pharmacological inhibition of Cdk4 may provide therapeutic benefit for NSCLC patients carrying K-RAS oncogenes. ..
- Haldar M, Karan G, Tvrdik P, Capecchi M. Two cell lineages, myf5 and myf5-independent, participate in mouse skeletal myogenesis. Dev Cell. 2008;14:437-45 pubmed publisher..We also demonstrate here the existence of a significant myf5 lineage within ribs that has an important role in rib development, suggested by severe rib defects upon ablating the myf5 lineage. ..
- Zhou Z, Shung C, Ota S, Akiyama H, Keene D, Hurlin P. Sequential and coordinated actions of c-Myc and N-Myc control appendicular skeletal development. PLoS ONE. 2011;6:e18795 pubmed publisher..Our results show that N-Myc and c-Myc act sequentially during limb development to coordinate the expansion of key progenitor populations responsible for forming the limb skeleton. ..
- Murphy M, Lawson J, Mathew S, Hutcheson D, Kardon G. Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration. Development. 2011;138:3625-37 pubmed publisher..Furthermore, we demonstrate that reciprocal interactions between fibroblasts and satellite cells contribute significantly to efficient, effective muscle regeneration...
- Le Garrec J, DomÃnguez J, Desgrange A, Ivanovitch K, RaphaÃ«l E, Bangham J, et al. A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics. elife. 2017;6: pubmed publisher..Our computer and quantitative tools provide novel insight into the mechanism of heart looping and the contribution of different factors, beyond the simple description of looping direction. This is relevant to congenital heart defects. ..
- Cisek L, Corden J. Phosphorylation of RNA polymerase by the murine homologue of the cell-cycle control protein cdc2. Nature. 1989;339:679-84 pubmed..This observation suggests a role for the cdc2 protein kinase in transcriptional regulation. ..
- Tokoro M, Shin S, Nishikawa S, Lee H, Hatanaka Y, Amano T, et al. Deposition of acetylated histones by RNAP II promoter clearance may occur at onset of zygotic gene activation in preimplantation mouse embryos. J Reprod Dev. 2010;56:607-15 pubmed
- Yuryev A, Patturajan M, Litingtung Y, Joshi R, Gentile C, Gebara M, et al. The C-terminal domain of the largest subunit of RNA polymerase II interacts with a novel set of serine/arginine-rich proteins. Proc Natl Acad Sci U S A. 1996;93:6975-80 pubmed..Thus, these results suggest that the CTD and a set of CTD-binding proteins may act to physically and functionally link transcription and pre-mRNA processing. ..