Dixon-McDougall Thomas, Brown Carolyn
Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Biochem Cell Biol. 2016 Feb;94(1):56-70. doi: 10.1139/bcb-2015-0016. Epub 2015 Jun 24.
During X-chromosome inactivation (XCI), nearly an entire X chromosome is permanently silenced and converted into a Barr body, providing dosage compensation for eutherians between the sexes. XCI is facilitated by the upregulation of the long non-coding RNA gene, XIST, which coats its chromosome of origin, recruits heterochromatin factors, and silences gene expression. During XCI, at least two distinct types of heterochromatin are established, and in this review we discuss the enrichment of facultative heterochromatin marks such as H3K27me3, H2AK119ub, and macroH2A as well as pericentric heterochromatin marks such as HP1, H3K9me3, and H4K20me3. The extremely stable maintenance of silencing is a product of reinforcing interactions within and between these domains. This paper "Xplores" the current knowledge of the pathways involved in XCI, how the pathways interact, and the gaps in our understanding that need to be filled.
在X染色体失活(XCI)过程中,几乎整条X染色体被永久沉默并转化为巴氏小体,从而实现了真兽亚纲两性之间的剂量补偿。长链非编码RNA基因XIST的上调促进了XCI,XIST覆盖其起源染色体,招募异染色质因子并使基因表达沉默。在XCI过程中,至少会形成两种不同类型的异染色质,在本综述中,我们讨论了兼性异染色质标记(如H3K27me3、H2AK119ub和macroH2A)以及着丝粒周围异染色质标记(如HP1、H3K9me3和H4K20me3)的富集情况。沉默的极其稳定的维持是这些结构域内部和之间增强相互作用的结果。本文“探索”了目前关于XCI所涉及途径的知识、这些途径如何相互作用以及我们理解中需要填补的空白。