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.
Differential patterns of histone methylation and acetylation distinguish active and repressed alleles at X-linked genes
Goto, Y.; Gomez, M.; Brockdorff, N.; Feil, R.
Cytogenet Genome Res
2002 / vol 99 / pages 66-74
71576 71576 [pii]
1424-859X (Electronic) 1424-8581 (Linking)
IGMM team(s) involved in this publication
Empreinte Génomique et Développement
Female; Animals; Mice; DNA Methylation; Gene Expression Regulation/*genetics; Male; Alleles; Methylation; Histones/*metabolism; RNA, Long Noncoding; Acetylation; Cell Line; Dosage Compensation, Genetic; Genetic Linkage; Hypoxanthine Phosphoribosyltransferase/genetics; Lysine/metabolism; Phosphoglycerate Kinase/genetics; RNA, Untranslated/genetics; Transcription Factors/genetics; X Chromosome/*genetics/metabolism