Title

Analysis of Neonatal Brain Lacking ATRX or MeCP2 Reveals Changes in Nucleosome Density, CTCF Binding and Chromatin Looping

Authors

Kristin D Kernohan
Douglas Vernimmen
Gregory B Gloor
Nathalie G. Bérubé, University of Western OntarioFollow

Document Type

Article

Publication Date

7-1-2014

Journal

Nucleic Acids Research

Volume

42

Issue

13

First Page

8356

Last Page

8368

URL with Digital Object Identifier

doi: 10.1093/nar/gku564

Abstract

ATRX and MeCP2 belong to an expanding group of chromatin-associated proteins implicated in human neurodevelopmental disorders, although their gene-regulatory activities are not fully resolved. Loss of ATRX prevents full repression of an imprinted gene network in the postnatal brain and in this study we address the mechanistic aspects of this regulation. We show that ATRX binds many imprinted domains individually but that transient co-localization between imprinted domains in the nuclei of neurons does not require ATRX. We demonstrate that MeCP2 is required for ATRX recruitment and that deficiency of either ATRX or MeCP2 causes decreased frequency of long-range chromatin interactions associated with altered nucleosome density at CTCF-binding sites and reduced CTCF occupancy. These findings indicate that MeCP2 and ATRX regulate gene expression at a subset of imprinted domains by maintaining a nucleosome configuration conducive to CTCF binding and to the maintenance of higher order chromatin structure.

Notes

PMID: 24990380