The long and the short of it: RNA‐directed chromatin asymmetry in mammalian X‐chromosome inactivation

Abstract

Edited by Ulrike KutayKeywords: X-chromosome inactivation xiRNA RNA interference Chromatin Xist Tsix a b s t r a c t 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.

Post-transcriptional gene silencing, transcriptional gene silencing and human immunodeficiency virus

“…In mammals, its establishment at a particular locus is a result of protein interactions and cross talk with multiple silencing mechanisms such as DNA methylation, genomic imprinting and Polycomb group of proteins (PcG) [65,103,110] . The epigenetic profiles across mammalian genomes are very heterogeneous and show a wide range of silencing dynamics.…”

“…During Xi, expression of the lncRNA Xist represses transcription from the paternal chromosome [110] . However, Xist is further regulated by the antisense lncRNA Tsix.…”

Epigenetics of imprinted long non-coding RNAs

“…11 On the other hand, Tsix expresses in the antisense orientation to Xist on the future active X chromosome (Xa) and silences the Xist expression in cis. [11][12][13] The functional role of long ncRNAs in the regulation of genomic imprinting was better illustrated in the case of Kcnq1ot1 and Air.…”

“…12 Tsix, whose promoter lies downstream of Xist transcription unit, transcribes the entire Xist gene in the antisense direction, and this correlates with the silencing of the overlapping Xist gene but not any other nonoverlapping genes. Several lines of recent evidence suggest a functional role for both Tsix RNA and/or its transcriptional process in the Tsix-mediated epigenetic inactivation of the Xist promoter on the future Xi.…”

Polycomb repressive complex 2 in embryonic stem cells: an overview

“…Chief among the epigenetic regulators of pluripotent gene expression and cell type transition are the Polycomb Group proteins (PcG). First identified in Drosophila as key repressors of Hox genes during body patterning, PcG proteins have been shown to play key roles in development, X-inactivation, cell pluripotency and somatic cell reprogramming (Schwartz and Pirrotta, 2007;Kanduri et al, 2009;Schuettengruber and Cavalli, 2009;Simon and Kingston, 2009;Surface et al, 2010).…”