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Composite macroH2A/NRF-1 Nucleosomes Suppress Noise and Generate Robustness in Gene Expression

ABSTRACT: The histone variant macroH2A has been implicated in transcriptional repression, but the molecular mechanisms that contribute to global macroH2A-dependent genome regulation remain elusive. Using ChIP-seq coupled with transcriptional profiling in macroH2A knock-down cells (GSE53103) we demonstrate that singular macroH2A nucleosomes occupy transcription start sites of subsets of both expressed and repressed genes with opposing regulatory consequences. Specifically macroH2A nucleosomes mask repressor binding sites in expressed genes, but activator binding sites in repressed genes thus generating distinct chromatin landscapes limiting genetic or extracellular inductive signals. We show that composite nucleosomes containing macroH2A and NRF-1 are stably positioned on gene regulatory regions and can buffer the transcriptional noise typifying antiviral responses. In contrast, macroH2A nucleosomes without NRF-1 bind promoters weakly and mark genes with noisier gene expression patterns. Thus, the strategic position and stabilization of macroH2A nucleosomes in human promoters defines robust gene expression patterns.

ORGANISM(S): Homo sapiens

PROVIDER: GSE53133 | GEO | 2015/05/06

SECONDARY ACCESSION(S): PRJNA230966

REPOSITORIES: GEO

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