Differential patterns of histone methylation and acetylation distinguish active and repressed alleles at X-linked genes.
In female mammals, one of the two X chromosomes is inactivated to compensate for the difference in dosage of X-linked genes between males and females. X inactivation involves sequential alterations to the chromatin that ultimately lead to the transcriptional repression of genes on the X chromosome. Here, histone methylation and acetylation along X-linked genes are investigated by chromatin immunoprecipitation (ChIP) of adult fibroblast cell lines. At PGK1 and HPRT, chromatin on the active X chromosome reveals H3 lysine 4 methylation and acetylation of histones H3 and H4. These modifications are absent on the repressed allele, which is marked by H3 lysine 9 methylation. On the expressed allele of XIST (on the inactive X chromosome), we found that H3 acetylation is confined to the promoter, whereas H3 lysine 4 methylation and H4 acetylation are present along the entire gene. On the repressed XIST allele, in contrast, the promoter and gene exhibit H3 lysine 9 methylation. At only 1.5 kb upstream of the XIST gene, chromatin on the inactive X chromosome has strongly reduced levels of H4 acetylation and is marked by both H3 lysine 9 and H3 lysine 4 methylation. These data demonstrate that patterns of histone methylation and acetylation are distinct along and upstream of XIST and suggest that the inactive X chromatin configuration occurs at a region close to the 5' end of the gene.
Goto
Y
Y
Institute of Molecular Genetics, CNRS, Montpellier, France.
Gomez
M
M
Brockdorff
N
N
Feil
R
R
D000107:Acetylation; D000483:Alleles; D000818:Animals; D002460:Cell Line; D019175:DNA Methylation; D004303:Dosage Compensation, Genetic; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D008040:Genetic Linkage; D006657:Histones / Q000378:metabolism*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008239:Lysine / Q000378:metabolism; D008297:Male; D008745:Methylation; D051379:Mice; D010735:Phosphoglycerate Kinase / Q000235:genetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014960:X Chromosome / Q000235:genetics* / Q000378:metabolism
D006657:Histones; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors; C465658:Tsix transcript, mouse; C077885:XIST non-coding RNA; D007041:Hypoxanthine Phosphoribosyltransferase; D010735:Phosphoglycerate Kinase; D008239:Lysine