Developmental regulation of Suz 12 localization.
Chromatin modifications are among the epigenetic alterations essential for genetic reprogramming during development. The Polycomb group (PcG) gene family mediates chromatin modifications that contribute to developmentally regulated transcriptional silencing. Trimethylation of histone H3 on lysine 27, mediated by a PcG protein complex consisting of Eed, Ezh2, and Suz12, is integral in differentiation, stem cell self-renewal, and tumorigenesis. Eed and Ezh2 are also implicated in the developmentally regulated silencing of the inactive X chromosome, as they are transiently enriched on the inactive X chromosome when X chromosome silencing is initiated. Here we analyze the dynamic localization of Suz12 during cellular differentiation and X-inactivation. Though Suz12 is a requisite member of the Eed/Ezh2 complexes, we found that Suz12 exhibits a notable difference from Ezh2 and Eed: while Ezh2 and Eed levels decrease during stem cell differentiation, Suz12 levels remain constant. Despite the differential regulation in abundance of Suz12 and Eed/Ezh2, Suz12 is also transiently enriched on the Xi during early stages of X-inactivation, and this accumulation is Xist RNA dependent. These results suggest that Suz12 may have a function that is not mediated by its association with Eed and Ezh2, and that this additional function is not involved in the regulation of X-inactivation.
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.
Cecile C
CC
de la Cruz
Jia
J
Fang
Kathrin
K
Plath
Kathleen A
KA
Worringer
Dmitri A
DA
Nusinow
Yi
Y
Zhang
Barbara
B
Panning
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics* / Q000502:physiology; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D051379:Mice; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D063151:Polycomb Repressive Complex 2; D011496:Protein Methyltransferases; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism; D049951:X Chromosome Inactivation
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C491488:EED protein, human; D006657:Histones; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C430461:SUZ12 protein, human; D014157:Transcription Factors; C077885:XIST non-coding RNA; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; C103523:EZH1 protein, human; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2