Expression noise and acetylation profiles distinguish HDAC functions.
Gene expression shows a significant variation (noise) between genetically identical cells. Noise depends on the gene expression process regulated by the chromatin environment. We screened for chromatin factors that modulate noise in S. cerevisiae and analyzed the results using a theoretical model that infers regulatory mechanisms from the noise versus mean relationship. Distinct activities of the Rpd3(L) and Set3 histone deacetylase complexes were predicted. Both HDACs repressed expression. Yet, Rpd3(L)C decreased the frequency of transcriptional bursts, while Set3C decreased the burst size, as did H2B monoubiquitination (ubH2B). We mapped the acetylation of H3 lysine 9 (H3K9ac) upon deletion of multiple subunits of Set3C and Rpd3(L)C and of ubH2B effectors. ubH2B and Set3C appear to function in the same pathway to reduce the probability that an elongating PolII produces a functional transcript (PolII processivity), while Rpd3(L)C likely represses gene expression at a step preceding elongation.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Leehee
L
Weinberger
Yoav
Y
Voichek
Itay
I
Tirosh
Gil
G
Hornung
Ido
I
Amit
Naama
N
Barkai
D000107:Acetylation; D001426:Bacterial Proteins / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015966:Gene Expression Regulation, Fungal; D015723:Gene Library; D055106:Genome-Wide Association Study; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000737:chemistry; D008164:Luminescent Proteins / Q000378:metabolism; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
D001426:Bacterial Proteins; D002843:Chromatin; D006657:Histones; D008164:Luminescent Proteins; D029701:Saccharomyces cerevisiae Proteins; C054562:yellow fluorescent protein, Bacteria; C511735:Set3 protein, S cerevisiae; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases