A chromodomain switch mediated by histone H3 Lys 4 acetylation regulates heterochromatin assembly
- Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom
Abstract
Chromodomain proteins (Chp1/Chp2/Swi6/Clr4) bind to methylated H3K9 (H3K9me) and regulate pericentric heterochromatin in fission yeast. Chp1 and Clr4 (H3K9-HMT), bind transcriptionally active heterochromatin, whereas Chp2/Swi6 (HP1 homologs) are recruited during the inactive state. We show that H3K4 acetylation (H3K4ac) plays a role in the transition of dimethylated H3K9 (H3K9me2) occupancy from Chp1/Clr4 to Chp2/Swi6. H3K4ac, mediated by Mst1, is enriched at pericentromeres concomitantly with heterochromatin reassembly. H3K4R (Lys → Arg) mutation increases Chp1 and decreases Chp2/Swi6 pericentric occupancy and exhibits centromeric desilencing. Consistent with structural data, H3K4ac specifically reduces Chp1/Clr4 affinity to H3K9me. We propose that H3K4ac mediates a chromodomain switch from Chp1/Clr4 to Swi6/Chp2 to allow heterochromatin reassembly.
Keywords
Footnotes
-
↵1 Corresponding author.
E-MAIL t.kouzarides{at}gurdon.cam.ac.uk; FAX 44-1223-334089.
-
Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1881710.
-
Supplemental material is available at http://www.genesdev.org.
-
- Received November 3, 2009.
- Accepted February 12, 2010.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press
