Yang Shi

..A model for the ER stress-mediated transcription factor binding and chromatin modifications at the Grp78 promoter leading to its activation is proposed...

..Taken together, our findings provide strong genetic evidence that the proapoptotic function of Par-4 is dependent on the cellular context and raise the possibility that alterations of Par-4 function may occur during carcinogenesis...

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..These findings identify a molecular mechanism by which CtBP mediates transcriptional repression and provide insight into CtBP participation in oncogenesis...

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..Our findings imply that in metazoans TFIID may be of widespread importance for transcription and for expression of tissue-specific genes...

..Our findings indicate that an imbalance of histone methylation dynamics has a critical role in XLMR...

..Our findings thus identify a family of H3K4me3 demethylases and uncover a critical link between histone modifications and XLMR...

..spr-5 mutants show no transcriptional misregulation of known DSBR involved genes. Instead, SPR-5 shows a rapid subcellular relocalization upon DSB-inducing treatment, which suggests that SPR-5 may function directly in DSBR...

..Taken together, these findings suggest that LSD1-mediated histone demethylation is regulated dynamically in vivo. This is expected to have profound effects on gene expression under both physiological and pathological conditions...

..Our findings identified a novel S. pombe histone demethylase with specificity toward di- and trimethylated histone H3-Lys-4 and a possible role in heterochromatin regulation...

..The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases...

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..These findings not only provide a novel insight into YY1 function but also identify a new regulation of homeotic protein-mediated transcriptional regulation in general...

..This was associated with H3K27 trimethylation leading to decreased gene expression and insulin signaling. These results have implications for rapamycin action in human diseases and biological processes such as longevity...

..Thus, REST is a key target in beta-TRCP-driven transformation and the beta-TRCP-REST axis is a new regulatory pathway controlling neurogenesis...

..Our finding that this family of demethylases generates different methylated states at the same lysine residue provides a mechanism for fine-tuning histone methylation...

..Taken together, these findings provide new insight into the mechanisms by which JMJD3 regulates gene expression...

..Taken together, these findings identify YY1 as a potential cofactor for Hdm2 in the regulation of p53 homeostasis and suggest a possible role for YY1 in tumorigenesis...

..Taken together, these findings identify a small family of H3K27 demethylases with important, evolutionarily conserved roles in H3K27 methylation regulation and in animal anterior-posterior development...

..Collectively, these observations reveal a link between YY1 and INO80 and roles for both in HRR, providing new insight into mechanisms that control the cellular response to genotoxic stress...

..X and 53BP1 foci formation. Our data provide a molecular mechanism by which ALKBH3 collaborates with ASCC to maintain genomic integrity in a cell-type specific manner...

..These results underscore the important role of YY1 in the maintenance of mitochondrial function and explain how its inactivation might contribute to exercise intolerance and mitochondrial myopathies...

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..We provide evidence that YY1 binds the intronic Ei mu enhancer within the IgH locus, consistent with a direct role for YY1 in V(H)D(H)J(H) recombination. These findings identified YY1 as a critical regulator of early B-cell development...

..These data not only shed new light on the molecular basis for YY1 developmental roles and cellular functions, but also provide insight into the general mechanisms controlling eukaryotic cell proliferation, apoptosis, and differentiation...

..Furthermore, our results provide the first evidence indicating that disrupting the read-out of histone modifications can cause an inherited human disease...

..These data provide a possible molecular mechanism linking LSD2 to transcriptional regulation after initiation...

..The chemical mechanisms and substrate specificities have already been extensively discussed elsewhere. This review focuses primarily on regulatory mechanisms that modulate demethylase recruitment and activity...

..Taken together, our data suggest that CTBP-1 controls life span probably through the regulation of lipid metabolism...

..Our study thus identifies the ET domain as a second important transcriptional regulatory domain for Brd4 in addition to the carboxyl-terminal domain (CTD) that interacts with pTEFb...

..elegans embryogenesis. The conservation of these lysines among other LEF/TCF family members suggests that acetylation may be an important, evolutionarily conserved mechanism regulating subcellular distribution of LEF/TCF factors...

..Our results suggest that polyglutamine expansions perturb transcription of CREB/CBP targets and that specific targeting of HDACs will be useful in reducing associated neurodegeneration...

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..SUMO-2-associated proteins identified in this study may contribute to SUMO-dependent regulation of transcription or other processes...

..Because human HDACs are targets for cancer therapy, these findings have significant implications in cancer treatment...

..Taken together, this study identifies an important role for YY1 in mouse meiosis and provides new insight into mechanisms that regulate mammalian spermatogenesis...

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..These findings identify hydroxylation as a post-translational modification important for Ago2 stability and effective RNA interference...

..These results define a biochemical mechanism by which the BRCA1 enzymatic activity regulates a key cellular process...

..Our results reveal ZNF335 as an essential link between H3K4 complexes and REST/NRSF and provide the first direct genetic evidence that this pathway regulates human neurogenesis and neuronal differentiation...

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..Trk receptor transactivation provides a mechanism by which diverse LRP1 ligands may show neurotrophic activity...

..These advances have also catalysed a resurgence of interest in epigenetic regulators as potential therapeutic targets...

..Inhibiting ERK/MAP kinase activation blocked expression of MCP-1. These studies support a model in which LRP1 regulates multiple aspects of Schwann cell physiology in the response to PNS injury...

..Our findings indicate that both normosmic IHH and KS are mild allelic variants of CHARGE syndrome and are caused by CHD7 mutations...

..We show that passenger strand cleavage and RNA chaperone activities that are intrinsic to both AGO1 and AGO2 are sufficient for RNA-induced silencing complex (RISC) loading...

..The importance of appropriately maintaining or reprogramming histone methylation is illustrated by its links to disease and ageing and possibly to transmission of traits across generations...

..These findings highlight the general utility of this DNA vector-based RNAi technology in suppressing gene expression in mammalian cells...

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..Here, we examine these and related facets of histone demethylases discovered to date, focusing on their biochemistry, structure, and enzymology...

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..In addition, our findings indicate that RNAi does operate in postmitotic mammalian neurons and thus offers a rapid genetic method of studying gene function in the development and function of the mammalian nervous system...

..Remarkably, Par-4DeltaLZ mice display significantly increased depression-like behaviors. Collectively, these results provide evidence that Par-4 constitutes a molecular link between impaired dopamine signaling and depression...

..Although siRNA delivery in vivo is a challenging problem, stable expression of siRNA, which targets oncogenic fusion genes, may potentiate the effects of conventional therapy for hematologic malignancies...

..In this review, we discuss recent studies on epigenetic regulation in MR and explore the concept of epigenetic therapy for MR...

..This Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 targets, ultimately contributing to mESC differentiation and the onset of embryonic development...

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..The KDM6 inhibitor shows remarkable substrate selectivity and can inhibit transcription of a plethora of pro-inflammatory genes in cell culture by altering H3K27me3 level at some of the KDM6 target genes...

..Our findings demonstrate that HAT activity is of primary importance for CBP-1 to regulate transcription and to promote differentiation during C. elegans embryogenesis...

..Our findings reveal a novel and specific function for the ubiquitously expressed HDA-1 in C. elegans gonadogenesis and place hda-1 in the Notch signaling pathway...

..This interaction may reflect the existence of coupling factors involved in CtBP-mediated transcriptional regulation and mRNA processing events...

..We suggest that Lid2 enzymatic activity in euchromatin is regulated through a dynamic interplay with other histone-modification enzymes. Our findings provide mechanistic insight into the coordination of H3K4 and H3K9 methylation...

..Sited-directed mutagenesis in conjunction with demethylase activity assays allowed us to propose a molecular model for substrate selection by the JMJD2 histone demethylase family...

..Together, our findings establish a pivotal role for trimethylation of H3K4 in gene repression and, potentially, tumour suppressor mechanisms...

..In addition, YY1 forms complexes with Ring1 and other class II PcG proteins such as Rnf2 and Bmi1 in GST pull down experiments in transfected cells. These findings provide evidence for a PcG function for YY1 in vertebrates...

..These results provide insights into the mechanisms and specificity of histone demethylation...

..Our results suggest a model whereby Wnt/MAPK signaling downregulates POP-1 levels in responsive cells, in part by increasing nuclear LIT-1 levels, thereby increasing POP-1 phosphorylation and PAR-5-mediated nuclear export...

..We conclude that the nuclear functions and physical interaction of Smad6 and CtBP provide a novel mechanism for the transcriptional regulation by inhibitory Smads...

..Thus, RNAi is a promising therapy for ALS and other disorders caused by dominant, gain-of-function gene mutations...

..Our study indicates that the ineffectiveness of HDAC inhibitors to induce apoptosis in NSCLC cancer cells is associated with the ability of these molecules to stimulate NF-kappa B-dependent transcription and cell survival...

..These findings reveal that LSD1 is targeted to chromatin by p53, likely in a gene-specific manner, and define a molecular mechanism by which p53 mediates transcription repression in vivo during differentiation...

..Thus, this enhanced U6 promoter is useful where limited choices of shRNA sequences preclude the selection of a highly efficient RNAi target region...

..Yy1 and Ctcf associate through specific protein-protein interactions and together transactivate Tsix. We propose that the Ctcf-Yy1-Tsix complex functions as a key component of the X chromosome binary switch...

..Thus, we identify YY1 as an essential component of the transcriptional network regulating the transition of oligodendrocyte progenitors from cell cycle exit to differentiation...

..Such chaperone-dependent signaling may play an important role in modulating the balance of *NO and O(2)(*) generation from eNOS and, therefore, vascular function...

..Many detection methods have been patented regarding probes and peptide used for identification of tumors...

..Our findings reveal a novel regulatory mechanism of vimentin transport during neurite extension that may have implications in diseases featuring transport/trafficking defects and impaired regeneration...

..These pathways may be responsible for cardioprotection in the chronically hypoxic infant rabbit heart...

..Findings will also shed new light on molecular mechanisms that control germ cell functions and will impact on our understanding of analogous processes in higher eukaryotes. ..

..elegans, and will shed significant new light on how their homologous proteins function in mammals. ..

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..Based on our strong initial results, new paradigms are likely to emerge from the proposed studies that will significantly impact our views of eukaryotic gene regulation. ..

..Based on our exciting initial results, the proposed studies are likely to result in new paradigms that will significantly impact our views of eukaryotic chromatin and transcriptional regulation. ..

..Finally, as an important step towards understanding the molecular mechanisms of transcriptional repression mediated by YY1, we will identify and clone target proteins for the repressor domain of YY1. ..

..elegans, and will shed light on how the homologous proteins p300 and CBP function in mammalian cells. ..

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