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Boxer, L.D.* ; Renthal, W.* ; Greben, A.W.* ; Whitwam, T.* ; Silberfeld, A.* ; Stroud, H.* ; Li, E.* ; Yang, M.G.* ; Kinde, B.* ; Griffith, E.C.* ; Bonev, B. ; Greenberg, M.E.*

MeCP2 represses the rate of transcriptional initiation of highly methylated long genes.

Mol. Cell 77, 294-309.e9 (2020)
Postprint Preprint Research data DOI PMC
Open Access Green
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Dna Methylation ; Mecp2 ; Ncor ; Rett Syndrome ; Rna Pol Ii ; Transcriptional Elongation ; Transcriptional Initiation; Rett-syndrome Mutations; Rna-seq; Dna-methylation; Molecular-basis; Read Alignment; Genome; Reveals; Expression; Sequence; Protein
Language english
Publication Year 2020
Prepublished in Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 1097-2765
e-ISSN 1097-4164
Journal Molecular Cell
Quellenangaben Volume: 77, Issue: 2, Pages: 294-309.e9 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Helmholtz Pioneer Campus (HPC)
POF-Topic(s) 30204 - Cell Programming and Repair
Research field(s) Pioneer Campus
PSP Element(s) G-510004-001
DOI 10.1016/j.molcel.2019.10.032
WOS ID WOS:000507859300011
Scopus ID 85077749982
PubMed ID 31784358
Erfassungsdatum 2020-01-22
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