title: Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome.
abstract: Almost 1-2% of the human genome is located within 500 bp of either side of a transcription initiation site, whereas a far larger proportion (approximately 25%) is potentially transcribable by elongating RNA polymerases. This observation raises the question of how the genome is packaged into chromatin to allow start sites to be recognized by the regulatory machinery at the same time as transcription initiation, but not elongation, is blocked in the 25% of intragenic DNA. We developed a chromatin scanning technique called ChAP, coupling the chromatin immunoprecipitation assay with arbitrarily primed PCR, which allows for the rapid and unbiased comparison of histone modification patterns within the eukaryotic nucleus. Methylated lysine 4 (K4) and acetylated K9/14 of histone H3 were both highly localized to the 5' regions of transcriptionally active human genes but were greatly decreased downstream of the start sites. Our results suggest that the large transcribed regions of human genes are maintained in a deacetylated conformation in regions read by elongating polymerase. Common models depicting widespread histone acetylation and K4 methylation throughout the transcribed unit do not therefore apply to the majority of human genes.
authors.affiliation: Department of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, MS 8302L, Los Angeles, CA 90089-9181. gliang@usc.edu
authors.forename: Gangning
authors.initials: G
authors.lastname: Liang
authors.forename: Joy C Y
authors.initials: JC
authors.lastname: Lin
authors.forename: Vivian
authors.initials: V
authors.lastname: Wei
authors.forename: Christine
authors.initials: C
authors.lastname: Yoo
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Cheng
authors.forename: Carvell T
authors.initials: CT
authors.lastname: Nguyen
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisenberger
authors.forename: Gerda
authors.initials: G
authors.lastname: Egger
authors.forename: Daiya
authors.initials: D
authors.lastname: Takai
authors.forename: Felicidad A
authors.initials: FA
authors.lastname: Gonzales
authors.forename: Peter A
authors.initials: PA
authors.lastname: Jones
mesh_terms: D000107:Acetylation; D019175:DNA Methylation; D015894:Genome, Human; D006657:Histones / Q000378:metabolism*; D006801:Humans; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D006657:Histones