Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex.
The yeast histone deacetylase Rpd3 can be recruited to promoters to repress transcription initiation. Biochemical, genetic, and gene-expression analyses show that Rpd3 exists in two distinct complexes. The smaller complex, Rpd3C(S), shares Sin3 and Ume1 with Rpd3C(L) but contains the unique subunits Rco1 and Eaf3. Rpd3C(S) mutants exhibit phenotypes remarkably similar to those of Set2, a histone methyltransferase associated with elongating RNA polymerase II. Chromatin immunoprecipitation and biochemical experiments indicate that the chromodomain of Eaf3 recruits Rpd3C(S) to nucleosomes methylated by Set2 on histone H3 lysine 36, leading to deacetylation of transcribed regions. This pathway apparently acts to negatively regulate transcription because deleting the genes for Set2 or Rpd3C(S) bypasses the requirement for the positive elongation factor Bur1/Bur2.
Keogh
Michael-Christopher
MC
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Kurdistani
Siavash K
SK
Morris
Stephanie A
SA
Ahn
Seong Hoon
SH
Podolny
Vladimir
V
Collins
Sean R
SR
Schuldiner
Maya
M
Chin
Kayu
K
Punna
Thanuja
T
Thompson
Natalie J
NJ
Boone
Charles
C
Emili
Andrew
A
Weissman
Jonathan S
JS
Hughes
Timothy R
TR
Strahl
Brian D
BD
Grunstein
Michael
M
Greenblatt
Jack F
JF
Buratowski
Stephen
S
Krogan
Nevan J
NJ
D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D016000:Cluster Analysis; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004843:Epistasis, Genetic; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism; D013489:Suppression, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D006657:Histones; D012097:Repressor Proteins; C071731:SIN3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D014157:Transcription Factors; D008780:Methyltransferases; C448996:Set2 protein, S cerevisiae; D000123:Acetyltransferases; C428131:Eaf3 protein, S cerevisiae; D018844:Cyclin-Dependent Kinases; C414163:SGV1 protein, S cerevisiae; D012319:RNA Polymerase II; C071665:RPD3 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases; D008239:Lysine