<p>In mammals, chromosome-wide regulatory mechanisms ensure a balance of X-linked gene dosage between males (XY) and females (XX). In female cells, expression of genes from one of the two X chromosomes is curtailed, with selective accumulation of Xist-RNA, Xist-associated proteins, specific histone modifications (for example, H3K27me3) and Barr body formation observed throughout interphase. Here we show, using chromosome flow-sorting, that during mitosis, Xist-associated proteins dissociate from inactive X (Xi) chromosomes, while high levels of H3K27me3 and increased compaction of the Xi relative to active X (Xa), are retained. Proteomic comparison of mitotic Xi and Xa revealed that components of Hbo1 and Msl/Mof histone acetyltransferase complexes are significantly enriched on Xa as compared to Xi and autosomes. By contrast, inhibitors of histone acetylation co-enrich with Xi. Furthermore, inhibition of Hbo1 or deletion of Msl/Mof components functionally abolishes mitotic differences in H3K27me3 marking and chromosome compaction. These data uncover critical roles for acetylation pathways in preserving X chromosome properties during mitosis.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Hbo1 and Msl complexes preserve differential compaction and H3K27me3 marking of active and inactive X chromosomes during mitosis

  • Dounia Djeghloul,
  • Sherry Cheriyamkunnel,
  • Bhavik Patel,
  • Holger Kramer,
  • Alex Montoya,
  • Karen E. Brown,
  • Chad Whilding,
  • Tatyana B. Nesterova,
  • Guifeng Wei,
  • Neil Brockdorff,
  • Iga Grządzielewska,
  • Remzi Karayol,
  • Asifa Akhtar,
  • Matthias Merkenschlager,
  • Amanda G. Fisher

摘要

In mammals, chromosome-wide regulatory mechanisms ensure a balance of X-linked gene dosage between males (XY) and females (XX). In female cells, expression of genes from one of the two X chromosomes is curtailed, with selective accumulation of Xist-RNA, Xist-associated proteins, specific histone modifications (for example, H3K27me3) and Barr body formation observed throughout interphase. Here we show, using chromosome flow-sorting, that during mitosis, Xist-associated proteins dissociate from inactive X (Xi) chromosomes, while high levels of H3K27me3 and increased compaction of the Xi relative to active X (Xa), are retained. Proteomic comparison of mitotic Xi and Xa revealed that components of Hbo1 and Msl/Mof histone acetyltransferase complexes are significantly enriched on Xa as compared to Xi and autosomes. By contrast, inhibitors of histone acetylation co-enrich with Xi. Furthermore, inhibition of Hbo1 or deletion of Msl/Mof components functionally abolishes mitotic differences in H3K27me3 marking and chromosome compaction. These data uncover critical roles for acetylation pathways in preserving X chromosome properties during mitosis.