Composite macroH2A/NRF-1 Nucleosomes Suppress Noise and Generate Robustness in Gene Expression.
Cell Rep
; 11(7): 1090-101, 2015 May 19.
Article
em En
| MEDLINE
| ID: mdl-25959814
ABSTRACT
The histone variant macroH2A (mH2A) has been implicated in transcriptional repression, but the molecular mechanisms that contribute to global mH2A-dependent genome regulation remain elusive. Using chromatin immunoprecipitation sequencing (ChIP-seq) coupled with transcriptional profiling in mH2A knockdown cells, we demonstrate that singular mH2A nucleosomes occupy transcription start sites of subsets of both expressed and repressed genes, with opposing regulatory consequences. Specifically, mH2A nucleosomes mask repressor binding sites in expressed genes but activator binding sites in repressed genes, thus generating distinct chromatin landscapes that limit genetic or extracellular inductive signals. We show that composite nucleosomes containing mH2A and NRF-1 are stably positioned on gene regulatory regions and can buffer transcriptional noise associated with antiviral responses. In contrast, mH2A nucleosomes without NRF-1 bind promoters weakly and mark genes with noisier gene expression patterns. Thus, the strategic position and stabilization of mH2A nucleosomes in human promoters defines robust gene expression patterns.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Histonas
/
Nucleossomos
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Regulação da Expressão Gênica
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Fator 1 Relacionado a NF-E2
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article