MeCP2 Represses the Rate of Transcriptional Initiation of Highly Methylated Long Genes.
DNA methylation
MeCP2
NCoR
RNA Pol II
Rett syndrome
transcriptional elongation
transcriptional initiation
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
16 01 2020
16 01 2020
Historique:
received:
26
02
2019
revised:
09
09
2019
accepted:
23
10
2019
pubmed:
1
12
2019
medline:
1
4
2020
entrez:
1
12
2019
Statut:
ppublish
Résumé
Mutations in the methyl-DNA-binding repressor protein MeCP2 cause the devastating neurodevelopmental disorder Rett syndrome. It has been challenging to understand how MeCP2 regulates transcription because MeCP2 binds broadly across the genome and MeCP2 mutations are associated with widespread small-magnitude changes in neuronal gene expression. We demonstrate here that MeCP2 represses nascent RNA transcription of highly methylated long genes in the brain through its interaction with the NCoR co-repressor complex. By measuring the rates of transcriptional initiation and elongation directly in the brain, we find that MeCP2 has no measurable effect on transcriptional elongation, but instead represses the rate at which Pol II initiates transcription of highly methylated long genes. These findings suggest a new model of MeCP2 function in which MeCP2 binds broadly across highly methylated regions of DNA, but acts at transcription start sites to attenuate transcriptional initiation.
Identifiants
pubmed: 31784358
pii: S1097-2765(19)30810-X
doi: 10.1016/j.molcel.2019.10.032
pmc: PMC6982532
mid: NIHMS1543679
pii:
doi:
Substances chimiques
Mecp2 protein, mouse
0
Methyl-CpG-Binding Protein 2
0
Repressor Proteins
0
RNA
63231-63-0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
294-309.e9Subventions
Organisme : NINDS NIH HHS
ID : F32 NS101739
Pays : United States
Organisme : NINDS NIH HHS
ID : K08 NS101064
Pays : United States
Organisme : NINDS NIH HHS
ID : K99 NS112415
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS048276
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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