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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.

Original publication

DOI

10.1159/000071576

Type

Journal article

Journal

Cytogenet Genome Res

Publication Date

2002

Volume

99

Pages

66 - 74

Keywords

Acetylation, Alleles, Animals, Cell Line, DNA Methylation, Dosage Compensation, Genetic, Female, Gene Expression Regulation, Genetic Linkage, Histones, Hypoxanthine Phosphoribosyltransferase, Lysine, Male, Methylation, Mice, Phosphoglycerate Kinase, RNA, Long Noncoding, RNA, Untranslated, Transcription Factors, X Chromosome