期刊
BIOLOGICAL CHEMISTRY
卷 389, 期 4, 页码 365-370出版社
WALTER DE GRUYTER & CO
DOI: 10.1515/BC.2008.046
关键词
chromatin; dosage compensation; histone methylation; immunofluorescence; metaphase chromosomes
资金
- Medical Research Council [G0300332] Funding Source: researchfish
- MRC [G0300332] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council Funding Source: Medline
- Cancer Research UK Funding Source: Medline
- Medical Research Council [G0300332] Funding Source: Medline
Silencing of genes on one of the two female X chromosomes early in development helps balance expression of X-linked genes between XX females and XY males and involves chromosome-wide changes in histone variants and modifications. Mouse female embryonic stem (ES) cells have two active Xs, one of which is silenced on differentiation, and provide a powerful model for studying the dynamics of X inactivation. Here, we use immunofluorescence microscopy of metaphase chromosomes to study changes in H3 mono-, di- or tri-methylated at lysine 4 (H3K4me1, -2 or -3) on the inactivating X (Xi) in female ES cells. H3K4me3 is absent from Xi in approximately 25% of chromosome spreads by day 2 of differentiation and in 40-50% of spreads by days 4-6, making it one of the earliest detectable changes on Xi. In contrast, loss of H3K4me2 occurs 1-2 days later, when histone acetylation also diminishes. Remarkably, H3K4me1 is depleted on both (active) X chromosomes in undifferentiated female ES cells, and on the single X in males, and remains depleted on Xi. Consistent with this, chromatin immunoprecipitation reveals differentiation-related reductions in H3K4me2 and H3K4me3 at the promoter regions of genes undergoing X-inactivation in female ES cells, but no comparable change in H3K4me1.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据