Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences

Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences

The heterogeneous collection of nucleosome remodelling and deacetylation (NuRD) complexes can be grouped into the MBD2- or MBD3-containing complexes MBD2–NuRD and MBD3–NuRD. MBD2 is known to bind to methylated CpG sequences in vitro in contrast to MBD3. Although functional differences have been desc...

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Main Authors: Günther, Katharina, Rust, Mareike, Leers, Joerg, Boettger, Thomas, Scharfe, Maren, Jarek, Michael, Bartkuhn, Marek, Renkawitz, Rainer
Format: Online
Language:English
Published: Oxford University Press 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597697/
id pubmed-3597697
recordtype oai_dc
spelling pubmed-35976972013-03-15 Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences Günther, Katharina Rust, Mareike Leers, Joerg Boettger, Thomas Scharfe, Maren Jarek, Michael Bartkuhn, Marek Renkawitz, Rainer Gene Regulation, Chromatin and Epigenetics The heterogeneous collection of nucleosome remodelling and deacetylation (NuRD) complexes can be grouped into the MBD2- or MBD3-containing complexes MBD2–NuRD and MBD3–NuRD. MBD2 is known to bind to methylated CpG sequences in vitro in contrast to MBD3. Although functional differences have been described, a direct comparison of MBD2 and MBD3 in respect to genome-wide binding and function has been lacking. Here, we show that MBD2–NuRD, in contrast to MBD3–NuRD, converts open chromatin with euchromatic histone modifications into tightly compacted chromatin with repressive histone marks. Genome-wide, a strong enrichment for MBD2 at methylated CpG sequences is found, whereas CpGs bound by MBD3 are devoid of methylation. MBD2-bound genes are generally lower expressed as compared with MBD3-bound genes. When depleting cells for MBD2, the MBD2-bound genes increase their activity, whereas MBD2 plus MBD3-bound genes reduce their activity. Most strikingly, MBD3 is enriched at active promoters, whereas MBD2 is bound at methylated promoters and enriched at exon sequences of active genes. Oxford University Press 2013-03 2013-01-29 /pmc/articles/PMC3597697/ /pubmed/23361464 http://dx.doi.org/10.1093/nar/gkt035 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Günther, Katharina
Rust, Mareike
Leers, Joerg
Boettger, Thomas
Scharfe, Maren
Jarek, Michael
Bartkuhn, Marek
Renkawitz, Rainer
spellingShingle Günther, Katharina
Rust, Mareike
Leers, Joerg
Boettger, Thomas
Scharfe, Maren
Jarek, Michael
Bartkuhn, Marek
Renkawitz, Rainer
Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences
author_facet Günther, Katharina
Rust, Mareike
Leers, Joerg
Boettger, Thomas
Scharfe, Maren
Jarek, Michael
Bartkuhn, Marek
Renkawitz, Rainer
author_sort Günther, Katharina
title Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences
title_short Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences
title_full Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences
title_fullStr Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences
title_full_unstemmed Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences
title_sort differential roles for mbd2 and mbd3 at methylated cpg islands, active promoters and binding to exon sequences
description The heterogeneous collection of nucleosome remodelling and deacetylation (NuRD) complexes can be grouped into the MBD2- or MBD3-containing complexes MBD2–NuRD and MBD3–NuRD. MBD2 is known to bind to methylated CpG sequences in vitro in contrast to MBD3. Although functional differences have been described, a direct comparison of MBD2 and MBD3 in respect to genome-wide binding and function has been lacking. Here, we show that MBD2–NuRD, in contrast to MBD3–NuRD, converts open chromatin with euchromatic histone modifications into tightly compacted chromatin with repressive histone marks. Genome-wide, a strong enrichment for MBD2 at methylated CpG sequences is found, whereas CpGs bound by MBD3 are devoid of methylation. MBD2-bound genes are generally lower expressed as compared with MBD3-bound genes. When depleting cells for MBD2, the MBD2-bound genes increase their activity, whereas MBD2 plus MBD3-bound genes reduce their activity. Most strikingly, MBD3 is enriched at active promoters, whereas MBD2 is bound at methylated promoters and enriched at exon sequences of active genes.
publisher Oxford University Press
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597697/
_version_ 1611962183920386048

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