Matches in SemOpenAlex for { <https://semopenalex.org/work/W146799703> ?p ?o ?g. }
- W146799703 abstract "It is evident that components of the 26S proteasome function beyond protein degradation in the regulation of transcription. Studies in yeast implicate the 26S proteasome, specifically the 19S cap, in the epigenetic regulation of transcription. Saccharomyces cerevisiae 19S ATPases remodel chromatin by facilitating histone acetylation and methylation. However, it is unclear if the 19S ATPases play similar roles in mammalian cells. We previously found that the 19S ATPase Sug1 positively regulates transcription of the critical inflammatory gene MHC-II and that the MHC-II promoter fails to efficiently bind transcription factors upon Sug1 knockdown. MHC-II transcription is regulated by the critical coactivator CIITA. We now find that Sug1 is crucial for regulating histone H3 acetylation at the cytokine inducible MHC-II and CIITA promoters. Histone H3 acetylation is dramatically decreased upon Sug1 knockdown with a preferential loss occurring at lysine 18. Research in yeast indicates that the ortholog of Sug1, Rpt6, acts as a mediator between the activating modifications of histone H2B ubiquitination and H3 methylation. Therefore, we characterized the role the 19S proteasome plays in regulating additional activating modifications. As with acetylation, Sug1 is necessary for proper histone H3K4 and H3R17 methylation at cytokine inducible promoters. In the absence of Sug1, histone H3K4me3 and H3R17me2 are substantially inhibited. Our observation that the loss of Sug1 has no significant effect on H3K36me3 implies that Sug1’s regulation of histone modifications is localized to promoter regions as H3K4me3 but not H3K36me3 is clustered around gene promoters. Here we show that multiple H3K4 histone methyltransferase subunits bind constitutively to the inducible MHC-II and CIITA promoters and that over-expressing one subunit significantly enhances promoter activity. Furthermore, we identified a critical subunit of the H3K4 methyltransferase complex that binds multiple histone modifying enzymes, but fails to bind the CIITA promoter in the absence of Sug1, implicating Sug1 in recruiting multi-enzyme complexes responsible for initiating transcription. Finally, Sug1 knockdown maintains gene silencing as elevated levels of H3K27 trimethylation are observed upon Sug1 knockdown. Together these studies strongly implicate the 19S proteasome in mediating the initial reorganization events to relax the repressive chromatin structure surrounding inducible genes. INDEX WORDS: Transcriptional regulation, Epigenetics, Histone modifications, Histone remodeling enzymes, Major histocompatibility complex class II, Class II transactivator, 26S proteasome, 19S proteasome, Sug1 THE EPIGENETIC REGULATION OF CYTOKINE INDUCIBLE MAMMALIAN TRANSCRIPTION BY THE 26S PROTEASOME" @default.
- W146799703 created "2016-06-24" @default.
- W146799703 creator A5081526082 @default.
- W146799703 date "2009-01-01" @default.
- W146799703 modified "2023-09-27" @default.
- W146799703 title "The Epigenetic Regulation of Cytokine Inducible Mammalian Transcription by the 26S Proteasome" @default.
- W146799703 cites W12673267 @default.
- W146799703 cites W1481011810 @default.
- W146799703 cites W1520976595 @default.
- W146799703 cites W1528845830 @default.
- W146799703 cites W1547600157 @default.
- W146799703 cites W1556364911 @default.
- W146799703 cites W1562107474 @default.
- W146799703 cites W1579847726 @default.
- W146799703 cites W1603793127 @default.
- W146799703 cites W1824777900 @default.
- W146799703 cites W1853154894 @default.
- W146799703 cites W1874881634 @default.
- W146799703 cites W1900657670 @default.
- W146799703 cites W1920211008 @default.
- W146799703 cites W1925763316 @default.
- W146799703 cites W1956285448 @default.
- W146799703 cites W1963996414 @default.
- W146799703 cites W1964096828 @default.
- W146799703 cites W1965260678 @default.
- W146799703 cites W1966266513 @default.
- W146799703 cites W1968455126 @default.
- W146799703 cites W1969077609 @default.
- W146799703 cites W1969691479 @default.
- W146799703 cites W1971921270 @default.
- W146799703 cites W1975497776 @default.
- W146799703 cites W1975962848 @default.
- W146799703 cites W1976195988 @default.
- W146799703 cites W1977121504 @default.
- W146799703 cites W1977836335 @default.
- W146799703 cites W1978077699 @default.
- W146799703 cites W1983861034 @default.
- W146799703 cites W1985063313 @default.
- W146799703 cites W1985562398 @default.
- W146799703 cites W1986301467 @default.
- W146799703 cites W1987195602 @default.
- W146799703 cites W1987932410 @default.
- W146799703 cites W1990594693 @default.
- W146799703 cites W1991475922 @default.
- W146799703 cites W1991667131 @default.
- W146799703 cites W1991930087 @default.
- W146799703 cites W1992182462 @default.
- W146799703 cites W1992518796 @default.
- W146799703 cites W1992662525 @default.
- W146799703 cites W1992741271 @default.
- W146799703 cites W1992868516 @default.
- W146799703 cites W1994196743 @default.
- W146799703 cites W1999284470 @default.
- W146799703 cites W2001113618 @default.
- W146799703 cites W2002466684 @default.
- W146799703 cites W2004333515 @default.
- W146799703 cites W2004988279 @default.
- W146799703 cites W2005635949 @default.
- W146799703 cites W2006463715 @default.
- W146799703 cites W2007684630 @default.
- W146799703 cites W2008735740 @default.
- W146799703 cites W2008922065 @default.
- W146799703 cites W2009533906 @default.
- W146799703 cites W2010524211 @default.
- W146799703 cites W2012326746 @default.
- W146799703 cites W2012425092 @default.
- W146799703 cites W2013092025 @default.
- W146799703 cites W2013339424 @default.
- W146799703 cites W2013844573 @default.
- W146799703 cites W2014179038 @default.
- W146799703 cites W2014782860 @default.
- W146799703 cites W2017188699 @default.
- W146799703 cites W2019642682 @default.
- W146799703 cites W2022936129 @default.
- W146799703 cites W2023348831 @default.
- W146799703 cites W2028003321 @default.
- W146799703 cites W2028691831 @default.
- W146799703 cites W2029572679 @default.
- W146799703 cites W2030023744 @default.
- W146799703 cites W2032449149 @default.
- W146799703 cites W2032493474 @default.
- W146799703 cites W2032736838 @default.
- W146799703 cites W2033691857 @default.
- W146799703 cites W2037168837 @default.
- W146799703 cites W2038473981 @default.
- W146799703 cites W2038580923 @default.
- W146799703 cites W2040375560 @default.
- W146799703 cites W2043295759 @default.
- W146799703 cites W2043817901 @default.
- W146799703 cites W2044551569 @default.
- W146799703 cites W2046006859 @default.
- W146799703 cites W2046717651 @default.
- W146799703 cites W2048599247 @default.
- W146799703 cites W2048670128 @default.
- W146799703 cites W2049170267 @default.
- W146799703 cites W2049647279 @default.
- W146799703 cites W2050018101 @default.
- W146799703 cites W2051003808 @default.
- W146799703 cites W2054205113 @default.
- W146799703 cites W2054621094 @default.