Gcn5 promotes acetylation, eviction, and methylation of nucleosomes in transcribed coding regions.
We report that coactivator SAGA, containing the HAT Gcn5p, occupies the GAL1 and ARG1 coding sequences during transcriptional induction, dependent on PIC assembly and Ser5 phosphorylation of the Pol II CTD. Induction of GAL1 increases H3 acetylation per nucleosome in the ORF, dependent on SAGA integrity but not the alternative Gcn5p-HAT complex ADA. Unexpectedly, H3 acetylation in ARG1 coding sequences does not increase during induction due to the opposing activities of multiple HDAs associated with the ORF. Remarkably, inactivation of Gcn5p decreases nucleosome eviction from both GAL1 and a long ( approximately 8 kb) ORF transcribed from the GAL1 promoter. This is associated with reduced Pol II occupancy at the 3' end and decreased mRNA production, selectively, for the long ORF. Gcn5p also enhances H3-K4 trimethylation in the ARG1 ORF and bulk histones. Thus, Gcn5p, most likely in SAGA, stimulates modification and eviction of nucleosomes in transcribed coding sequences and promotes Pol II elongation.
Govind
Chhabi K
CK
Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
Zhang
Fan
F
Qiu
Hongfang
H
Hofmeyer
Kimberly
K
Hinnebusch
Alan G
AG
D000107:Acetylation; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008745:Methylation; D009707:Nucleosomes / Q000378:metabolism*; D016366:Open Reading Frames / Q000235:genetics*; D010749:Phosphoprotein Phosphatases; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D039221:mRNA Cleavage and Polyadenylation Factors; D000099224:p300-CBP-Associated Factor
D002352:Carrier Proteins; D018844:Cyclin-Dependent Kinases; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D006657:Histones; D009707:Nucleosomes; D010749:Phosphoprotein Phosphatases; D010768:Phosphoserine; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D039221:mRNA Cleavage and Polyadenylation Factors; C507785:SAGA complex, S cerevisiae; C416934:SSU72 protein, S cerevisiae; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor; C084210:Kin28 protein kinase, S cerevisiae