Cargando…
Analysis of neonatal brain lacking ATRX or MeCP2 reveals changes in nucleosome density, CTCF binding and chromatin looping
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...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117782/ https://www.ncbi.nlm.nih.gov/pubmed/24990380 http://dx.doi.org/10.1093/nar/gku564 |
_version_ | 1782328748097404928 |
---|---|
author | Kernohan, Kristin D. Vernimmen, Douglas Gloor, Gregory B. Bérubé, Nathalie G. |
author_facet | Kernohan, Kristin D. Vernimmen, Douglas Gloor, Gregory B. Bérubé, Nathalie G. |
author_sort | Kernohan, Kristin D. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4117782 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41177822014-08-15 Analysis of neonatal brain lacking ATRX or MeCP2 reveals changes in nucleosome density, CTCF binding and chromatin looping Kernohan, Kristin D. Vernimmen, Douglas Gloor, Gregory B. Bérubé, Nathalie G. Nucleic Acids Res Gene regulation, Chromatin and Epigenetics 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. Oxford University Press 2014-09-01 2014-07-18 /pmc/articles/PMC4117782/ /pubmed/24990380 http://dx.doi.org/10.1093/nar/gku564 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Gene regulation, Chromatin and Epigenetics Kernohan, Kristin D. Vernimmen, Douglas Gloor, Gregory B. Bérubé, Nathalie G. Analysis of neonatal brain lacking ATRX or MeCP2 reveals changes in nucleosome density, CTCF binding and chromatin looping |
title | Analysis of neonatal brain lacking ATRX or MeCP2 reveals changes in nucleosome density, CTCF binding and chromatin looping |
title_full | Analysis of neonatal brain lacking ATRX or MeCP2 reveals changes in nucleosome density, CTCF binding and chromatin looping |
title_fullStr | Analysis of neonatal brain lacking ATRX or MeCP2 reveals changes in nucleosome density, CTCF binding and chromatin looping |
title_full_unstemmed | Analysis of neonatal brain lacking ATRX or MeCP2 reveals changes in nucleosome density, CTCF binding and chromatin looping |
title_short | Analysis of neonatal brain lacking ATRX or MeCP2 reveals changes in nucleosome density, CTCF binding and chromatin looping |
title_sort | analysis of neonatal brain lacking atrx or mecp2 reveals changes in nucleosome density, ctcf binding and chromatin looping |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117782/ https://www.ncbi.nlm.nih.gov/pubmed/24990380 http://dx.doi.org/10.1093/nar/gku564 |
work_keys_str_mv | AT kernohankristind analysisofneonatalbrainlackingatrxormecp2revealschangesinnucleosomedensityctcfbindingandchromatinlooping AT vernimmendouglas analysisofneonatalbrainlackingatrxormecp2revealschangesinnucleosomedensityctcfbindingandchromatinlooping AT gloorgregoryb analysisofneonatalbrainlackingatrxormecp2revealschangesinnucleosomedensityctcfbindingandchromatinlooping AT berubenathalieg analysisofneonatalbrainlackingatrxormecp2revealschangesinnucleosomedensityctcfbindingandchromatinlooping |