title: H3K4 tri-methylation provides an epigenetic signature of active enhancers.
abstract: Combinations of post-translational histone modifications shape the chromatin landscape during cell development in eukaryotes. However, little is known about the modifications exactly delineating functionally engaged regulatory elements. For example, although histone H3 lysine 4 mono-methylation (H3K4me1) indicates the presence of transcriptional gene enhancers, it does not provide clearcut information about their actual position and stage-specific activity. Histone marks were, therefore, studied here at genomic loci differentially expressed in early stages of T-lymphocyte development. The concomitant presence of the three H3K4 methylation states (H3K4me1/2/3) was found to clearly reflect the activity of bona fide T-cell gene enhancers. Globally, gain or loss of H3K4me2/3 at distal genomic regions correlated with, respectively, the induction or the repression of associated genes during T-cell development. In the Tcrb gene enhancer, the H3K4me3-to-H3K4me1 ratio decreases with the enhancer's strength. Lastly, enhancer association of RNA-polymerase II (Pol II) correlated with the presence of H3K4me3 and Pol II accumulation resulted in local increase of H3K4me3. Our results suggest the existence of functional links between Pol II occupancy, H3K4me3 enrichment and enhancer activity.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Parc Scientifique de Luminy, Case 906, Marseille, France.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Pekowska
authors.forename: Touati
authors.initials: T
authors.lastname: Benoukraf
authors.forename: Joaquin
authors.initials: J
authors.lastname: Zacarias-Cabeza
authors.forename: Mohamed
authors.initials: M
authors.lastname: Belhocine
authors.forename: Frederic
authors.initials: F
authors.lastname: Koch
authors.forename: Hélène
authors.initials: H
authors.lastname: Holota
authors.forename: Jean
authors.initials: J
authors.lastname: Imbert
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Andrau
authors.forename: Pierre
authors.initials: P
authors.lastname: Ferrier
authors.forename: Salvatore
authors.initials: S
authors.lastname: Spicuglia
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D002460:Cell Line; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D019674:Genes, T-Cell Receptor beta; D006657:Histones / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D008239:Lysine / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012319:RNA Polymerase II / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000254:growth & development / Q000378:metabolism
chemical_list: D017252:CD3 Complex; C485468:Cd3e protein, mouse; D006657:Histones; D012319:RNA Polymerase II; D008239:Lysine