Methylation of histone H3 at Lys-9 is an early mark on the X chromosome during X inactivation.
Coating of the X chromosome by Xist RNA is an essential trigger for X inactivation. However, little is known about the early chromatin remodeling events that transform this signal into transcriptional silencing. Here we report that methylation of histone H3 lysine 9 on the inactive X chromosome occurs immediately after Xist RNA coating and before transcriptional inactivation of X-linked genes. X-chromosomal H3 Lys-9 methylation occurs during the same window of time as H3 Lys-9 hypoacetylation and H3 Lys-4 hypomethylation. Histone H3 modifications thus represent the earliest known chromatin changes during X inactivation. We also identify a unique "hotspot" of H3 Lys-9 methylation 5' to Xist, and we propose that this acts as a nucleation center for Xist RNA-dependent spread of inactivation along the X chromosome via H3 Lys-9 methylation.
Heard
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Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. edith.heard@curie.fr
Rougeulle
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Arnaud
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Avner
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Allis
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Spector
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D054758:A Kinase Anchor Proteins; D000107:Acetylation; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004303:Dosage Compensation, Genetic; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051783:Methyl-CpG-Binding Protein 2; D008745:Methylation; D051379:Mice; D015778:Minor Histocompatibility Antigens; D008954:Models, Biological; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012313:RNA / Q000378:metabolism; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D013234:Stem Cells / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D014960:X Chromosome / Q000378:metabolism*
D054758:A Kinase Anchor Proteins; C085467:AKAP13 protein, human; D048868:Adaptor Proteins, Signal Transducing; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006657:Histones; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D015778:Minor Histocompatibility Antigens; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C077885:XIST non-coding RNA; D050760:Cyclin-Dependent Kinase Inhibitor p27; D012313:RNA