Xist RNA repeat E is essential for ASH2L recruitment to the inactive X and regulates histone modifications and escape gene expression
Yue M. Ogawa A. Yamada N. Charles Richard J.L. Barski A. Ogawa Y.
Yue M.
Ogawa A.
Yamada N.
Barski A.
Ogawa Y.
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Alternative Title
Abstract
Long non-coding RNA Xist plays a crucial role in establishing and maintaining X-chromosome inactivation (XCI) which is a paradigm of long non-coding RNA-mediated gene regulation. Xist has Xist-specific repeat elements A-F which are conserved among eutherian mammals, underscoring their functional importance. Here we report that Xist RNA repeat E, a conserved Xist repeat element in the Xist exon 7, interacts with ASH2L and contributes to maintenance of escape gene expression level on the inactive X-chromosome (Xi) during XCI. The Xist repeat E-deletion mutant female ES cells show the depletion of ASH2L from the Xi upon differentiation. Furthermore, a subset of escape genes exhibits unexpectedly higher expression in the repeat E mutant cells than the cells expressing wildtype Xist during X-inactivation, whereas the silencing of X-linked non-escape genes is not affected. We discuss the implications of these results to understand the role of ASH2L and Xist repeat E for histone modifications and escape gene regulation during random X-chromosome inactivation. © 2017 Yue et al.
Keywords
long non coding RNA Xist, long untranslated RNA, membrane protein, protein ASH2L, unclassified drug, Ash2l protein, mouse, DNA binding protein, long untranslated RNA, nuclear protein, transcription factor, XIST non-coding RNA, animal cell, Article, chromatin immunoprecipitation, controlled study, endothelium cell, enzyme localization, epigenetics, exon, female, gene control, gene expression, gene inactivation, half life time, histone modification, immunoprecipitation, mouse, nonhuman, protein depletion, protein RNA binding, quantitative analysis, reverse transcription polymerase chain reaction, upregulation, animal, biosynthesis, cell differentiation, embryonic stem cell, gene deletion, gene expression regulation, gene silencing, genetic transcription, genetics, histone code, metabolism, X chromosome, X chromosome inactivation, Animals, Cell Differentiation, DNA-Binding Proteins, Embryonic Stem Cells, Exons, Gene Deletion, Gene Expression Regulation, Gene Silencing, Histone Code, Mice, Nuclear Proteins, RNA, Long Noncoding, Transcription Factors, Transcription, Genetic, X Chromosome, X Chromosome Inactivation
Source Title
PLoS Genetics
Publisher
Public Library of Science
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Date
2017
DOI
10.1371/journal.pgen.1006890
Type
Article