Methylation of histone H3 K4 mediates association of the Isw1p ATPase with chromatin.
Set1p methylates lysine 4 (K4) of histone H3 and regulates the expression of many genes in yeast. Here we use a biochemical approach to identify a protein, Isw1p, which recognizes chromatin preferentially when it is di- and trimethylated at K4 H3. We show that on certain actively transcribed genes, the Isw1p chromatin remodeling ATPase requires K4 H3 methylation to associate with chromatin in vivo. Analysis of one such gene, MET16, shows that the enzymatic activities of Set1p and Isw1p are functionally connected: Set1p methylation and Isw1p ATPase generate specific chromatin changes at the 5' end of the gene, are necessary for the correct distribution of RNA polymerase II over the coding region, and are required for the recruitment of the cleavage and polyadenylation factor Rna15p. These results indicate that K4 H3 methylation and Isw1p ATPase activity are intimately linked in regulating transcription of certain genes in yeast.
Santos-Rosa
Helena
H
Wellcome Trust/Cancer Research UK Institute and Department of Pathology, Tennis Court Road, Cambridge CB2 1QR, United Kingdom.
Schneider
Robert
R
Bernstein
Bradley E
BE
Karabetsou
Nickoletta
N
Morillon
Antonin
A
Weise
Christoph
C
Schreiber
Stuart L
SL
Mellor
Jane
J
Kouzarides
Tony
T
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D008745:Methylation; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; D008715:Methionine; D012319:RNA Polymerase II; D000251:Adenosine Triphosphatases; C470546:ISW1 protein, S cerevisiae; C409462:SMARCA5 protein, human; D008239:Lysine