The long and the short of it: RNA-directed chromatin asymmetry in mammalian X-chromosome inactivation |
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Authors: | Chandrasekhar Kanduri Joanne Whitehead |
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Institution: | a Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammarskjölds Väg 20, 75185 Uppsala, Sweden b Mechanics and Genetics of Embryonic and Tumoural Development, UMR168, Institut Curie/CNRS, 75005 Paris, France |
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Abstract: | Mammalian X-chromosome inactivation is controlled by a multilayered silencing pathway involving both short and long non-coding RNAs, which differentially recruit the epigenetic machinery to establish chromatin asymmetries. In response to developmentally regulated small RNAs, dicer, a key effector of RNA interference, locally silences Xist on the active X-chromosome and establishes the heterochromatin conformation along the silent X-chromosome. The 1.6 kb RepA RNA initiates silencing by targeting the PRC2 polycomb complex to the inactive X-chromosome. In addition, the nuclear microenvironment is implicated in the initiation and maintenance of X-chromosome asymmetries. Here we review new findings involving these various RNA species in terms of understanding Xist gene regulation and the establishment of X-chromosome inactivation. |
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Keywords: | X-chromosome inactivation xiRNA RNA interference Chromatin Xist Tsix |
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