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Karger Publishers, Cytogenetic and Genome Research, 1-4(99), p. 66-74, 2002

DOI: 10.1159/000071576

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Differential patterns of histone methylation and acetylation distinguish active and repressed alleles at X-linked genes

Journal article published in 2002 by Y. Goto, M. Gomez, N. Brockdorff, R. Feil ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

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 <i>Pgk1</i> and <i>Hprt,</i> 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 <i>Xist</i> (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 <i>Xist</i> allele, in contrast, the promoter and gene exhibit H3 lysine 9 methylation. At only 1.5 kb upstream of the <i>Xist</i> 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 <i>Xist</i> and suggest that the inactive X chromatin configuration occurs at a region close to the 5′ end of the gene.