MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system.

The high level of 5-hydroxymethylcytosine (5hmC) present in neuronal genomes suggests that mechanisms interpreting 5hmC in the CNS may differ from those present in embryonic stem cells. Here, we present quantitative, genome-wide analysis of 5hmC, 5-methylcytosine (5mC), and gene expression in differ...

Popoln opis

Bibliografske podrobnosti
Main Authors: Mellén, M, Ayata, P, Dewell, S, Kriaucionis, S, Heintz, N
Format: Journal article
Jezik:English
Izdano: 2012
_version_ 1826285226523885568
author Mellén, M
Ayata, P
Dewell, S
Kriaucionis, S
Heintz, N
author_facet Mellén, M
Ayata, P
Dewell, S
Kriaucionis, S
Heintz, N
author_sort Mellén, M
collection OXFORD
description The high level of 5-hydroxymethylcytosine (5hmC) present in neuronal genomes suggests that mechanisms interpreting 5hmC in the CNS may differ from those present in embryonic stem cells. Here, we present quantitative, genome-wide analysis of 5hmC, 5-methylcytosine (5mC), and gene expression in differentiated CNS cell types in vivo. We report that 5hmC is enriched in active genes and that, surprisingly, strong depletion of 5mC is observed over these regions. The contribution of these epigenetic marks to gene expression depends critically on cell type. We identify methyl-CpG-binding protein 2 (MeCP2) as the major 5hmC-binding protein in the brain and demonstrate that MeCP2 binds 5hmC- and 5mC-containing DNA with similar high affinities. The Rett-syndrome-causing mutation R133C preferentially inhibits 5hmC binding. These findings support a model in which 5hmC and MeCP2 constitute a cell-specific epigenetic mechanism for regulation of chromatin structure and gene expression.
first_indexed 2024-03-07T01:25:40Z
format Journal article
id oxford-uuid:91e5d1d6-cb3f-4ed9-945f-c61e7a540f31
institution University of Oxford
language English
last_indexed 2024-03-07T01:25:40Z
publishDate 2012
record_format dspace
spelling oxford-uuid:91e5d1d6-cb3f-4ed9-945f-c61e7a540f312022-03-26T23:21:42ZMeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:91e5d1d6-cb3f-4ed9-945f-c61e7a540f31EnglishSymplectic Elements at Oxford2012Mellén, MAyata, PDewell, SKriaucionis, SHeintz, NThe high level of 5-hydroxymethylcytosine (5hmC) present in neuronal genomes suggests that mechanisms interpreting 5hmC in the CNS may differ from those present in embryonic stem cells. Here, we present quantitative, genome-wide analysis of 5hmC, 5-methylcytosine (5mC), and gene expression in differentiated CNS cell types in vivo. We report that 5hmC is enriched in active genes and that, surprisingly, strong depletion of 5mC is observed over these regions. The contribution of these epigenetic marks to gene expression depends critically on cell type. We identify methyl-CpG-binding protein 2 (MeCP2) as the major 5hmC-binding protein in the brain and demonstrate that MeCP2 binds 5hmC- and 5mC-containing DNA with similar high affinities. The Rett-syndrome-causing mutation R133C preferentially inhibits 5hmC binding. These findings support a model in which 5hmC and MeCP2 constitute a cell-specific epigenetic mechanism for regulation of chromatin structure and gene expression.
spellingShingle Mellén, M
Ayata, P
Dewell, S
Kriaucionis, S
Heintz, N
MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system.
title MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system.
title_full MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system.
title_fullStr MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system.
title_full_unstemmed MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system.
title_short MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system.
title_sort mecp2 binds to 5hmc enriched within active genes and accessible chromatin in the nervous system
work_keys_str_mv AT mellenm mecp2bindsto5hmcenrichedwithinactivegenesandaccessiblechromatininthenervoussystem
AT ayatap mecp2bindsto5hmcenrichedwithinactivegenesandaccessiblechromatininthenervoussystem
AT dewells mecp2bindsto5hmcenrichedwithinactivegenesandaccessiblechromatininthenervoussystem
AT kriaucioniss mecp2bindsto5hmcenrichedwithinactivegenesandaccessiblechromatininthenervoussystem
AT heintzn mecp2bindsto5hmcenrichedwithinactivegenesandaccessiblechromatininthenervoussystem