Genomes and Genes
Gene Symbol: Hbb-y
Description: hemoglobin Y, beta-like embryonic chain
Alias: Hby, hemoglobin subunit epsilon-Y2, epsilon Y globin, epsilon-Y2-globin, hemoglobin epsilon-Y2 chain
- Ben Zur T, Wides R. Mapping homologs of Drosophila odd Oz (odz): Doc4/Odz4 to mouse chromosome 7, Odz1 to mouse chromosome 11; and ODZ3 to human chromosome Xq25. Genomics. 1999;58:102-3 pubmed
- Zhang M, Zhu X, Zhang Y, Cai Y, Chen J, Sivaprakasam S, et al. RCAD/Ufl1, a Ufm1 E3 ligase, is essential for hematopoietic stem cell function and murine hematopoiesis. Cell Death Differ. 2015;22:1922-34 pubmed publisher..The finding of RCAD/Ufl1 as a key regulator of cellular stress response sheds a light into the role of a novel protein network including RCAD/Ufl1 and its associated proteins in regulating cellular homeostasis. ..
- Elorza A, Hyde B, Mikkola H, Collins S, Shirihai O. UCP2 modulates cell proliferation through the MAPK/ERK pathway during erythropoiesis and has no effect on heme biosynthesis. J Biol Chem. 2008;283:30461-70 pubmed publisher..Together, these results indicate that UCP2 is a regulator of erythropoiesis and suggests that inhibition of UCP2 function may contribute to the development of anemia. ..
- Perkins A, Sharpe A, Orkin S. Lethal beta-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF. Nature. 1995;375:318-22 pubmed..Its stage-specific and beta-globin-gene-specific requirement suggests that EKLF may facilitate completion of the fetal-to-adult (haemoglobin gamma to beta) switch in humans. ..
- Yoon D, Pastore Y, Divoky V, Liu E, Mlodnicka A, Rainey K, et al. Hypoxia-inducible factor-1 deficiency results in dysregulated erythropoiesis signaling and iron homeostasis in mouse development. J Biol Chem. 2006;281:25703-11 pubmed..These results identify a novel role for HIF-1 in the regulation of iron homeostasis and reveal unexpected regulatory differences in Epo/EpoR signaling in yolk sac and embryonic erythropoiesis. ..
- Chen W, Gu P, Jiang X, Ruan H, Li C, Gao X. Protein phosphatase 2A catalytic subunit ? (PP2Ac?) maintains survival of committed erythroid cells in fetal liver erythropoiesis through the STAT5 pathway. Am J Pathol. 2011;178:2333-43 pubmed publisher..Collectively, these data provide direct loss-of-function evidence demonstrating the importance of PP2Ac? for the survival of committed erythroid cells during fetal liver erythropoiesis...
- Trepicchio W, Dyer M, Baron M. A novel developmental regulatory motif required for stage-specific activation of the epsilon-globin gene and nuclear factor binding in embryonic erythroid cells. Mol Cell Biol. 1994;14:3763-71 pubmed..Several lines of evidence suggest that the binding factors in embryonic and adult erythroid cells are distinguished by posttranscriptional differences. ..
- Eferl R, Sibilia M, Hilberg F, Fuchsbichler A, Kufferath I, Guertl B, et al. Functions of c-Jun in liver and heart development. J Cell Biol. 1999;145:1049-61 pubmed
- Hansen J, Konkel D, Leder P. The sequence of a mouse embryonic beta-globin gene. Evolution of the gene and its signal region. J Biol Chem. 1982;257:1048-52 pubmed..As expected from evolutionary considerations, it is more homologous to human embryonic beta-globin than to mouse adult beta-globin. ..
- Liu X, Li X, Wang Y, Shu R, Wang L, Lu S, et al. Disruption of palladin leads to defects in definitive erythropoiesis by interfering with erythroblastic island formation in mouse fetal liver. Blood. 2007;110:870-6 pubmed..These data demonstrate that palladin is crucial for definitive erythropoiesis and erythroblastic island formation and, especially, required for normal function of macrophages in fetal liver. ..
- Stern R, Russell E, Taylor B. Strain distribution and linkage relationship of a mouse embryonic hemoglobin variant. Biochem Genet. 1976;14:373-81 pubmed..019. ..
- Pang C, Lemsaddek W, Alhashem Y, Bondzi C, Redmond L, Ah Son N, et al. Kruppel-like factor 1 (KLF1), KLF2, and Myc control a regulatory network essential for embryonic erythropoiesis. Mol Cell Biol. 2012;32:2628-44 pubmed publisher..5 and E11.5. This study reveals a novel regulatory network by which KLF1 and KLF2 regulate Myc to control the primitive erythropoietic program. ..
- Hu X, Bulger M, Roach J, Eszterhas S, Olivier E, Bouhassira E, et al. Promoters of the murine embryonic beta-like globin genes Ey and betah1 do not compete for interaction with the beta-globin locus control region. Proc Natl Acad Sci U S A. 2003;100:1111-5 pubmed..The implication of these findings for models of beta-globin gene expression are discussed. ..
- Shimizu R, Trainor C, Nishikawa K, Kobayashi M, Ohneda K, Yamamoto M. GATA-1 self-association controls erythroid development in vivo. J Biol Chem. 2007;282:15862-71 pubmed..These results provide the first convincing line of evidence that the self-association of GATA-1 is important for proper mammalian erythroid development in vivo. ..
- Lopez R, Schoetz S, DeAngelis K, O NEILL D, Bank A. Multiple hematopoietic defects and delayed globin switching in Ikaros null mice. Proc Natl Acad Sci U S A. 2002;99:602-7 pubmed..These results indicate that Ikaros and PYR complex function together in vivo at many adult hematopoietic cell-specific genes and at intergenic sites, affecting their expression and leading to pleiotropic hematopoietic defects. ..
- Nuez B, Michalovich D, Bygrave A, Ploemacher R, Grosveld F. Defective haematopoiesis in fetal liver resulting from inactivation of the EKLF gene. Nature. 1995;375:316-8 pubmed..Enucleated erythrocytes are formed but these do not contain the proper amount of haemoglobin. We conclude that the transcription factor EKLF is essential for the final steps of definitive erythropoiesis in fetal liver. ..
- Hosoya Ohmura S, Mochizuki N, Suzuki M, Ohneda O, Ohneda K, Yamamoto M. GATA-4 incompletely substitutes for GATA-1 in promoting both primitive and definitive erythropoiesis in vivo. J Biol Chem. 2006;281:32820-30 pubmed..These data thus show a functional incompatibility between hematopoietic and endodermal GATA factors in vivo and provide evidence indicating specific roles of the C-terminal region of GATA-1 in primitive erythropoiesis. ..
- Marin M, Karis A, Visser P, Grosveld F, Philipsen S. Transcription factor Sp1 is essential for early embryonic development but dispensable for cell growth and differentiation. Cell. 1997;89:619-28 pubmed..MeCP2 is thought to be required for the maintenance of differentiated cells. We suggest that Sp1 is an important regulator of this process. ..
- Whitney J. Differential control of the synthesis of two hemoglobin beta chains in normal mice. Cell. 1977;12:863-71 pubmed
- Affara N, Goldfarb P, Vass K, Lyons A, Harrison P. Cloning of a new mouse foetal beta-globin mRNA sequence. Nucleic Acids Res. 1981;9:3061-75 pubmed..of pFG5 confirms that it does not code for the beta major or beta minor globin chains nor the embryonic epsilon Y2 globin chain; but it is identical to the published partial sequence of the epsilon Y3 globin gene over the region ..
- Hu X, Eszterhas S, Pallazzi N, Bouhassira E, Fields J, Tanabe O, et al. Transcriptional interference among the murine beta-like globin genes. Blood. 2007;109:2210-6 pubmed
- Porcu S, Poddie D, Melis M, Cao A, Ristaldi M. beta-Minor globin gene expression is preferentially reduced in EKLF Knock-Out mice. Gene. 2005;351:11-7 pubmed..The results obtained support a general role of EKLF in beta-globin gene activation and are in agreement with models involving an advantage of the LCR proximal respect to distal gene. ..
- Douglas K, Camper S. Partial transcriptome of the developing pituitary gland. Genomics. 2000;70:335-46 pubmed..The tissue distribution, cell specificity, and developmental regulation were determined for a subset of the transcripts. ..
- Miccio A, Blobel G. Role of the GATA-1/FOG-1/NuRD pathway in the expression of human beta-like globin genes. Mol Cell Biol. 2010;30:3460-70 pubmed publisher..These results suggest that, unexpectedly, NuRD is required for FOG-1-dependent activation of adult-type globin gene expression but is dispensable for human gamma-globin silencing in vivo. ..
- Römer I, Jungblut P, Reik W, Otto A, Klose J. A novel strategy to identify maternal and paternal inheritance in the mouse. Electrophoresis. 1995;16:823-30 pubmed..For the beta-group hemoglobins our results suggested parental effects on the transcriptional level. ..
- Bultman S, Gebuhr T, Magnuson T. A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in beta-globin expression and erythroid development. Genes Dev. 2005;19:2849-61 pubmed..Not only does this mutation establish a role for Brg1 during organogenesis, it also demonstrates that ATPase activity can be uncoupled from chromatin remodeling. ..
- Yasuda Y, Sasaki T, Takagawa M, Maeda M, Yasuda M, Atsumi T, et al. Erythropoietin contributes to implantation: ectopic hemoglobin synthesis in decidual cells of mice. Congenit Anom (Kyoto). 2007;47:22-33 pubmed..This is the first evidence that ectopic Hb synthesis exists and that erythropoietin coregulates erythroid (globin) and nonerythroid (delta-aminolevulinate synthase) genes. ..
- Orelio C, Dzierzak E. Identification of 2 novel genes developmentally regulated in the mouse aorta-gonad-mesonephros region. Blood. 2003;101:2246-9 pubmed..The identification of differentially expressed genes in the AGM region should yield further insights into the development of this tissue and into the emergence and regulation of HSCs...
- Jahn C, Hutchison C, Phillips S, Weaver S, Haigwood N, Voliva C, et al. DNA sequence organization of the beta-globin complex in the BALB/c mouse. Cell. 1980;21:159-68 pubmed..The rest of this sequence is intact, resembling an adult beta-globin gene except for an inserted base at cocon 90, resulting in a frameshift. Consequently, the beta h3 sequence cannot be translated to produce a normal beta-globin. ..
- Shou S, Scott V, Reed C, Hitzemann R, Stadler H. Transcriptome analysis of the murine forelimb and hindlimb autopod. Dev Dyn. 2005;234:74-89 pubmed..05) suggesting that by E 12.5, unique gene combinations are being used during the differentiation of each autopod type. ..
- Kingsley P, Malik J, Emerson R, Bushnell T, McGrath K, Bloedorn L, et al. "Maturational" globin switching in primary primitive erythroid cells. Blood. 2006;107:1665-72 pubmed..Globin switching during ontogeny is due not only to the sequential appearance of primitive and definitive lineages but also to changes in globin expression as primitive erythroblasts mature in the bloodstream. ..
- Griffin C, Brennan J, Magnuson T. The chromatin-remodeling enzyme BRG1 plays an essential role in primitive erythropoiesis and vascular development. Development. 2008;135:493-500 pubmed
- Todokoro K, Ikawa Y. Sequential expression of proto-oncogenes during a mouse erythroleukemia cell differentiation. Biochem Biophys Res Commun. 1986;135:1112-8 pubmed..The expression of ten other proto-oncogenes examined here were not detected, nor dramatically changed during differentiation process. ..
- Basu P, Lung T, Lemsaddek W, Sargent T, Williams D, Basu M, et al. EKLF and KLF2 have compensatory roles in embryonic beta-globin gene expression and primitive erythropoiesis. Blood. 2007;110:3417-25 pubmed..The data indicate that EKLF and KLF2 have redundant functions in embryonic beta-like globin gene expression, primitive erythropoiesis, and endothelial development. ..
- Shivdasani R, Mayer E, Orkin S. Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL. Nature. 1995;373:432-4 pubmed..Profound reduction in myeloid cells cultured in vivo from tal-1 null yolk sacs suggests a broader defect manifest at the myelo-erythroid or multipotential progenitor cell level. ..
- Kawane K, Fukuyama H, Kondoh G, Takeda J, Ohsawa Y, Uchiyama Y, et al. Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver. Science. 2001;292:1546-9 pubmed..Thus, DNase II in macrophages appears to be responsible for destroying the nuclear DNA expelled from erythroid precursor cells. ..
- Fromm G, de Vries C, Byron R, Fields J, Fiering S, Groudine M, et al. Histone hyperacetylation within the beta-globin locus is context-dependent and precedes high-level gene expression. Blood. 2009;114:3479-88 pubmed publisher..These data narrow the range of possible mechanisms by which hyperacetylated domains form. ..
- Strouboulis J, Dillon N, Grosveld F. Developmental regulation of a complete 70-kb human beta-globin locus in transgenic mice. Genes Dev. 1992;6:1857-64 pubmed..These results suggest that multiple changes in DNA sequences and transcription factor balance must have occurred for the human gamma-globin gene to have evolved into a fetal gene. ..
- Papadopoulos P, GutiÃ©rrez L, Demmers J, Scheer E, Pourfarzad F, Papageorgiou D, et al. TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis. Mol Cell Biol. 2015;35:2103-18 pubmed publisher..Thus, our findings demonstrate a cross talk between canonical TFIID and SAGA complexes and cell-specific transcription activators during development and differentiation. ..
- Bulger M, van Doorninck J, Saitoh N, Telling A, Farrell C, Bender M, et al. Conservation of sequence and structure flanking the mouse and human beta-globin loci: the beta-globin genes are embedded within an array of odorant receptor genes. Proc Natl Acad Sci U S A. 1999;96:5129-34 pubmed
- Ema M, Yokomizo T, Wakamatsu A, Terunuma T, Yamamoto M, Takahashi S. Primitive erythropoiesis from mesodermal precursors expressing VE-cadherin, PECAM-1, Tie2, endoglin, and CD34 in the mouse embryo. Blood. 2006;108:4018-24 pubmed..The latter cell population includes progenitors that give rise to primitive hematopoietic cells, suggesting that primitive and definitive hematopoietic cells in the mouse embryo arise from EC marker-positive cells. ..
- Yu T, Thomas D, Zhu W, Goodman M, Gumucio D. Regulation of fetal versus embryonic gamma globin genes: appropriate developmental stage expression patterns in the presence of HS2 of the locus control region. Blood. 2002;99:1082-4 pubmed
- Wilkinson D, Bailes J, Champion J, McMahon A. A molecular analysis of mouse development from 8 to 10 days post coitum detects changes only in embryonic globin expression. Development. 1987;99:493-500 pubmed..c. Thus the only abundant transcripts and corresponding proteins that change over a period of profound morphogenetic change correspond to globins of the newly established blood system. ..
- Yagishita N, Ohneda K, Amano T, Yamasaki S, Sugiura A, Tsuchimochi K, et al. Essential role of synoviolin in embryogenesis. J Biol Chem. 2005;280:7909-16 pubmed..Our findings emphasized the indispensable role of the Synoviolin in embryogenesis. ..
- Dyer M, Farrington S, Mohn D, Munday J, Baron M. Indian hedgehog activates hematopoiesis and vasculogenesis and can respecify prospective neurectodermal cell fate in the mouse embryo. Development. 2001;128:1717-30 pubmed..To our knowledge, these are the earliest functions for a hedgehog protein in post-implantation development in the mouse embryo. ..
- Beck L, Leroy C, Beck Cormier S, Forand A, Salaun C, Paris N, et al. The phosphate transporter PiT1 (Slc20a1) revealed as a new essential gene for mouse liver development. PLoS ONE. 2010;5:e9148 pubmed publisher..This work is the first to illustrate a specific in vivo role for PiT1 by uncovering it as being a critical gene for normal developmental liver growth. ..
- Peraki I, Palis J, Mavrothalassitis G. The Ets2 Repressor Factor (Erf) Is Required for Effective Primitive and Definitive Hematopoiesis. Mol Cell Biol. 2017;37: pubmed publisher..We conclude that Erf is required for both primitive and erythromyeloid progenitor waves of hematopoietic stem cell (HSC)-independent hematopoiesis as well as for the normal function of HSCs. ..
- Dahm K, Nielsen P, Muller A. Transcripts of Fliz1, a nuclear zinc finger protein, are expressed in discrete foci of the murine fetal liver. Genomics. 2001;73:194-202 pubmed..Nuclear localization studies revealed that Fliz1 is targeted to the nucleus. Thus, Fliz1 is a newly identified nuclear protein expressed in hematopoietic progenitor cells of the developing fetal liver. ..
- Wada J, Kumar A, Ota K, Wallner E, Batlle D, Kanwar Y. Representational difference analysis of cDNA of genes expressed in embryonic kidney. Kidney Int. 1997;51:1629-38 pubmed
- Fiering S, Epner E, Robinson K, Zhuang Y, Telling A, Hu M, et al. Targeted deletion of 5'HS2 of the murine beta-globin LCR reveals that it is not essential for proper regulation of the beta-globin locus. Genes Dev. 1995;9:2203-13 pubmed..In addition, this result emphasizes that when using homologous recombination to analyze complex regulatory elements in vivo, the inserted selectable marker must be removed to avoid influencing the phenotype of the mutation. ..
- Keng V, Yagi H, Ikawa M, Nagano T, Myint Z, Yamada K, et al. Homeobox gene Hex is essential for onset of mouse embryonic liver development and differentiation of the monocyte lineage. Biochem Biophys Res Commun. 2000;276:1155-61 pubmed..These results indicate that Hex plays an essential role in progenitor cells which commit to the hepatic endoderm and in the hematopoietic differentiation of the monocyte lineage. ..
- Itoh F, Itoh S, Carvalho R, Adachi T, Ema M, Goumans M, et al. Poor vessel formation in embryos from knock-in mice expressing ALK5 with L45 loop mutation defective in Smad activation. Lab Invest. 2009;89:800-10 pubmed publisher..This study supports our earlier observation that vascular maturation in vivo requires both TGF-beta/ALK1/BMP-Smad and TGF-beta/ALK5/activin-Smad pathways for normal vascular development. ..
- Alhashem Y, Vinjamur D, Basu M, Klingmuller U, Gaensler K, Lloyd J. Transcription factors KLF1 and KLF2 positively regulate embryonic and fetal beta-globin genes through direct promoter binding. J Biol Chem. 2011;286:24819-27 pubmed publisher..Therefore, KLF1 and KLF2 positively regulate the embryonic and fetal ?-globin genes through direct promoter binding. KLF1 is required for normal histone modifications in the ?-globin locus in mouse embryos. ..
- Casavant N, Hardies S, Funk F, Comer M, Edgell M, Hutchison C. Extensive movement of LINES ONE sequences in beta-globin loci of Mus caroli and Mus domesticus. Mol Cell Biol. 1988;8:4669-74 pubmed..L1 insertions may be the predominant cause of restriction fragment length polymorphisms in closely related haplotypes. ..
- Vanin E, Farace M, Gambari R, Fantoni A. The nucleotide sequence of the mouse embryonic beta-like y-globin messenger RNA as determined from cloned cDNA. Gene. 1981;16:141-8 pubmed..160 million years (MY) ago and that the embryonic-fetal duplication occurred approx. 100 MY ago. ..
- Seo K, Kon Y, Watanabe T. Embryonic hematopoiesis defect in the tattered-Hokkaido (Tdho) mouse. Comp Med. 2000;50:27-31 pubmed..5 Tdho male embryos. Furthermore, diminished numbers of anucleated erythrocytes were observed in E12.5 mutant embryos. A defect of embryonic hematopoiesis in Tdho mice was suggested as one of the possible causes of embryo lethality. ..
- Niki M, Okada H, Takano H, Kuno J, Tani K, Hibino H, et al. Hematopoiesis in the fetal liver is impaired by targeted mutagenesis of a gene encoding a non-DNA binding subunit of the transcription factor, polyomavirus enhancer binding protein 2/core binding factor. Proc Natl Acad Sci U S A. 1997;94:5697-702 pubmed..Thus, the results indicate that the two subunits function together as a heterodimeric PEBP2/CBF in vivo and that PEBP2/CBF plays an essential role in the development of definitive hematopoiesis. ..
- Holdener Kenny B, Weaver S. A naturally occurring deletion in the mouse Hbbs beta-globin gene cluster. Proc Natl Acad Sci U S A. 1986;83:4374-8 pubmed..We propose that the Hbb-bh0 gene is a recently disabled pseudogene. ..
- England S, McGrath K, Frame J, Palis J. Immature erythroblasts with extensive ex vivo self-renewal capacity emerge from the early mammalian fetus. Blood. 2011;117:2708-17 pubmed publisher..Extensively self-renewing erythroblasts, despite their near complete maturity within the hematopoietic hierarchy, may ultimately serve as a renewable source of red cells for transfusion therapy...
- Belaoussoff M, Farrington S, Baron M. Hematopoietic induction and respecification of A-P identity by visceral endoderm signaling in the mouse embryo. Development. 1998;125:5009-18 pubmed..Therefore, primitive endoderm signaling is a critical early determinant of hematopoietic and vascular development and plays a decisive role in anterior-posterior patterning during mouse embryogenesis. ..
- Hug B, Wesselschmidt R, Fiering S, Bender M, Epner E, Groudine M, et al. Analysis of mice containing a targeted deletion of beta-globin locus control region 5' hypersensitive site 3. Mol Cell Biol. 1996;16:2906-12 pubmed
- Yang D, Ma Z, Lin W, Yang J, Tian C, Wei H, et al. Identification of KAP-1-associated complexes negatively regulating the Ey and ?-major globin genes in the ?-globin locus. J Proteomics. 2013;80:132-44 pubmed publisher..We found that KAP-1 may contribute to the repression of Ey and ?-major globin gene transcription through recruitment to the promoters of these two genes, mediated by the interaction of KAP-1 with either Zfp445 or MafK, respectively. ..
- Baron M, Farrington S. Positive regulators of the lineage-specific transcription factor GATA-1 in differentiating erythroid cells. Mol Cell Biol. 1994;14:3108-14 pubmed
- Nakajima O, Takahashi S, Harigae H, Furuyama K, Hayashi N, Sassa S, et al. Heme deficiency in erythroid lineage causes differentiation arrest and cytoplasmic iron overload. EMBO J. 1999;18:6282-9 pubmed..These results demonstrate that ALAS-E, and hence heme supply, is necessary for differentiation and iron metabolism of erythroid cells. ..
- Tondeleir D, Drogat B, Slowicka K, Bakkali K, Bartunkova S, Goossens S, et al. Beta-Actin Is Involved in Modulating Erythropoiesis during Development by Fine-Tuning Gata2 Expression Levels. PLoS ONE. 2013;8:e67855 pubmed publisher..These results provide new molecular insights for a novel function of beta-actin in erythropoiesis by modulating the expression levels of Gata2 in vivo. ..
- McGrath K, Frame J, Fromm G, Koniski A, Kingsley P, Little J, et al. A transient definitive erythroid lineage with unique regulation of the ?-globin locus in the mammalian embryo. Blood. 2011;117:4600-8 pubmed publisher..We conclude that yolk sac-derived EMPs, the first of 2 origins of definitive erythropoiesis, express a unique pattern of globin genes as they generate the first definitive erythrocytes in the liver of the mammalian embryo...
- Brooke Bisschop T, Savory J, Foley T, Ringuette R, Lohnes D. Essential roles for Cdx in murine primitive hematopoiesis. Dev Biol. 2017;422:115-124 pubmed publisher..These findings demonstrate critical roles for Cdx members in murine primitive hematopoiesis upstream of Scl. ..