Chromatin context and ncRNA highlight targets of MeCP2 in brain

Scott S. Maxwell, Gregory J Pelka, Patrick P L Tam, Assam El-Osta

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

Abstract

The discovery that Rett syndrome (RTT) is caused by mutation of the methyl-CpG-binding-protein MeCP2 provided a major breakthrough in understanding the neurodevelopmental disorder and accelerated MeCP2 research. However, gene regulation by MeCP2 is complicated. The current consensus for MeCP2 remains as a classical repressor complex, with major emphasis on its role in methylation-dependent binding and repression. However, recent evidence indicates additional regulatory roles, suggesting non-classical mechanisms in gene activation. This has opened the field of MeCP2 research and suggests that the gene targets may not be the usual suspects, that is, dependent only on DNA methylation. Here we examine how chromatin binding and sequence preference may confer MeCP2 functionality, and connect relevant pathways in an active genome. Finding both genomic and proteomic evidence to indicate MeCP2 spliceosome interaction, we consequently discovered broad MeCP2 enrichment of the transcriptome while our focus toward long non-coding RNA (lncRNA) revealed MeCP2 association with RNCR3. Our data may indicate an as-yet-unappreciated role between lncRNA and MeCP2. We hypothesize that ncRNA may mediate chromatin-remodeling events by interacting with MeCP2, thereby conferring changes in gene expression. We consider that these results may suggest new mechanisms of gene regulation conferred by MeCP2 and its interactions upon chromatin structure and gene function.

Original languageEnglish
Pages (from-to)1741-1757
Number of pages17
JournalRNA Biology
Volume10
Issue number11
DOIs
Publication statusPublished - Nov 2013

Keywords

  • MeCP2
  • chromatin
  • gene expression
  • DNA methylation
  • spliceosome
  • ncRNA

Cite this

Maxwell, Scott S. ; Pelka, Gregory J ; Tam, Patrick P L ; El-Osta, Assam. / Chromatin context and ncRNA highlight targets of MeCP2 in brain. In: RNA Biology. 2013 ; Vol. 10, No. 11. pp. 1741-1757.
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Chromatin context and ncRNA highlight targets of MeCP2 in brain. / Maxwell, Scott S.; Pelka, Gregory J; Tam, Patrick P L; El-Osta, Assam.

In: RNA Biology, Vol. 10, No. 11, 11.2013, p. 1741-1757.

Research output: Contribution to journalArticleResearchpeer-review

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