Differential patterns of histone methylation and acetylation distinguish active and repressed alleles at X-linked genes (original) (raw)
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2002
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Cytogenetics and Cell Genetics
Research Articles| August 14 2003
aInstitute of Molecular Genetics, CNRS, Montpellier (France); and
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bX Inactivation Group, MRC Clinical Sciences Centre, ICSM, Hammersmith Hospital, London (UK)
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bX Inactivation Group, MRC Clinical Sciences Centre, ICSM, Hammersmith Hospital, London (UK)
Search for other works by this author on:
aInstitute of Molecular Genetics, CNRS, Montpellier (France); and
Search for other works by this author on:
Cytogenetics and Cell Genetics (2002) 99 (1-4): 66–74.
Received:
November 20 2002
Accepted:
February 06 2003
Published Online:
August 14 2003
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 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.
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© 2003 S. Karger AG, Basel
2003
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