title: Composite macroH2A/NRF-1 Nucleosomes Suppress Noise and Generate Robustness in Gene Expression.
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.
authors.affiliation: Biomedical Research Foundation, Academy of Athens, 4 Soranou Efesiou Street, Athens 11527, Greece.
authors.forename: Matthieu D
authors.initials: MD
authors.lastname: Lavigne
authors.affiliation: Biomedical Research Foundation, Academy of Athens, 4 Soranou Efesiou Street, Athens 11527, Greece.
authors.forename: Giannis
authors.initials: G
authors.lastname: Vatsellas
authors.affiliation: Biomedical Research Foundation, Academy of Athens, 4 Soranou Efesiou Street, Athens 11527, Greece.
authors.forename: Alexander
authors.initials: A
authors.lastname: Polyzos
authors.affiliation: Biomedical Research Foundation, Academy of Athens, 4 Soranou Efesiou Street, Athens 11527, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Mantouvalou
authors.affiliation: Biomedical Research Foundation, Academy of Athens, 4 Soranou Efesiou Street, Athens 11527, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Sianidis
authors.affiliation: Biomedical Research Foundation, Academy of Athens, 4 Soranou Efesiou Street, Athens 11527, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Maraziotis
authors.affiliation: Biomedical Research Foundation, Academy of Athens, 4 Soranou Efesiou Street, Athens 11527, Greece.
authors.forename: Marios
authors.initials: M
authors.lastname: Agelopoulos
authors.affiliation: Biomedical Research Foundation, Academy of Athens, 4 Soranou Efesiou Street, Athens 11527, Greece. Electronic address: thanos@bioacademy.gr.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Thanos
mesh_terms: D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000235:genetics*; D006801:Humans; D051265:NF-E2-Related Factor 1 / Q000235:genetics*; D009707:Nucleosomes / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D006657:Histones; D051265:NF-E2-Related Factor 1; D009707:Nucleosomes; C120756:macroH2A histone