title: Transcriptional inhibition of genes with severe histone h3 hypoacetylation in the coding region.
abstract: Changes in histone acetylation at promoters correlate with transcriptional activation and repression, but whether acetylation of histones in the coding region of genes is important for transcription is less clear. Here, we show that cells lacking the histone acetyltransferases Gcn5 and Elp3 have widespread and severe histone H3 hypoacetylation in chromatin. Surprisingly, severe hypoacetylation in the promoter does not invariably affect the ability of TBP to bind the TATA element, or transcription of the gene. By contrast, similar hypoacetylation of the coding region correlates with inhibition of transcription, and inhibition correlates better with the overall charge of the histone H3 tail than with hypoacetylation of specific lysine residues. These data provide insights into the effects of histone H3 hypoacetylation in vivo and underscore the importance of the overall charge of the histone tail for transcription.
authors.affiliation: Mechanisms of Transcription Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, EN6 3LD, Hertfordshire, United Kingdom.
authors.forename: Arnold
authors.initials: A
authors.lastname: Kristjuhan
authors.forename: Jane
authors.initials: J
authors.lastname: Walker
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Suka
authors.forename: Michael
authors.initials: M
authors.lastname: Grunstein
authors.forename: Douglas
authors.initials: D
authors.lastname: Roberts
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Cairns
authors.forename: Jesper Q
authors.initials: JQ
authors.lastname: Svejstrup
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics; D004268:DNA-Binding Proteins; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D005800:Genes, Fungal / Q000235:genetics*; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism*; D009154:Mutation; D016366:Open Reading Frames / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics; D012319:RNA Polymerase II / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D016385:TATA Box / Q000235:genetics; D035181:TATA-Box Binding Protein / Q000378:metabolism; D014158:Transcription, Genetic; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D011494:Protein Kinases; D012319:RNA Polymerase II; D029701:Saccharomyces cerevisiae Proteins; D035181:TATA-Box Binding Protein; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor