title: Multilayered chromatin analysis reveals E2f, Smad and Zfx as transcriptional regulators of histones.
abstract: Histones, the building blocks of eukaryotic chromatin, are essential for genome packaging, function and regulation. However, little is known about their transcriptional regulation. Here we conducted a comprehensive computational analysis, based on chromatin immunoprecipitation-sequencing and -microarray analysis (ChIP-seq and ChIP-chip) data of over 50 transcription factors and histone modifications in mouse embryonic stem cells. Enrichment scores supported by gene expression data from gene knockout studies identified E2f1 and E2f4 as master regulators of histone genes, CTCF and Zfx as repressors of core and linker histones, respectively, and Smad1, Smad2, YY1 and Ep300 as restricted or cell type-specific regulators. We propose that histone gene regulation is substantially more complex than previously thought, and that a combination of factors orchestrate histone gene regulation, from strict synchronization with S phase to targeted regulation of specific histone subtypes.
authors.affiliation: Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Gokhman
authors.forename: Ilana
authors.initials: I
authors.lastname: Livyatan
authors.forename: Badi Sri
authors.initials: BS
authors.lastname: Sailaja
authors.forename: Shai
authors.initials: S
authors.lastname: Melcer
authors.forename: Eran
authors.initials: E
authors.lastname: Meshorer
mesh_terms: D000818:Animals; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000378:metabolism; D050704:E2F4 Transcription Factor / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D012097:Repressor Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D051898:Smad1 Protein / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D050986:YY1 Transcription Factor / Q000378:metabolism
chemical_list: D000076246:CCCTC-Binding Factor; D002843:Chromatin; C000619698:Ctcf protein, mouse; D050687:E2F1 Transcription Factor; D050704:E2F4 Transcription Factor; C493754:E2f1 protein, mouse; C493763:E2f4 protein, mouse; D006657:Histones; D051741:Kruppel-Like Transcription Factors; D012097:Repressor Proteins; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse; C062076:zinc finger protein, X-linked; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse