SUV39 SET domains mediate crosstalk of heterochromatic histone marks.

Alessandro StirpeThomas Schalch


The SUV39 class of methyltransferase enzymes deposits histone H3 lysine 9 di- and trimethylation (H3K9me2/3), the hallmark of constitutive heterochromatin. How these enzymes are regulated to mark specific genomic regions as heterochromatic is poorly understood. Clr4 is the sole H3K9me2/3 methyltransferase in the fission yeast Schizosaccharomyces pombe, and recent evidence suggests that ubiquitination of lysine 14 on histone H3 (H3K14ub) plays a key role in H3K9 methylation. However, the molecular mechanism of this regulation and its role in heterochromatin formation remain to be determined. Our structure-function approach shows that the H3K14ub substrate binds specifically and tightly to the catalytic domain of Clr4, and thereby stimulates the enzyme by over 250-fold. Mutations that disrupt this mechanism lead to a loss of H3K9me2/3 and abolish heterochromatin silencing similar to clr4 deletion. Comparison with mammalian SET domain proteins suggests that the Clr4 SET domain harbors a conserved sensor for H3K14ub, which mediates licensing of heterochromatin formation.


Oct 22, 2002·Nature Structural Biology·Jinrong MinRui-Ming Xu
Feb 13, 2003·Journal of the American Chemical Society·Cyril DominguezAlexandre M J J Bonvin
Oct 17, 2003·Current Biology : CB·Barbara G MelloneRobin C Allshire
Jan 6, 2004·Science·André VerdelDanesh Moazed
Aug 10, 2005·Genome Biology·Shane C DillonXiaodong Cheng
Mar 1, 2006·BMC Bioinformatics·Joshua S YuanC Neal Stewart
Oct 3, 2006·Cellular and Molecular Life Sciences : CMLS·C Qian, M-M Zhou
Mar 18, 2008·Nature Structural & Molecular Biology·Ke ZhangShiv I S Grewal
Apr 14, 2009·Nature Methods·Daniel G GibsonHamilton O Smith
May 16, 2009·Proceedings of the National Academy of Sciences of the United States of America·Tamás FischerShiv I S Grewal
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Alexei Vagin, Alexei Teplyakov
Jan 20, 2010·PloS One·Hong WuMatthieu Schapira
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Mar 9, 2010·Current Opinion in Genetics & Development·Shiv Is Grewal
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Garib N MurshudovAlexei A Vagin
Nov 15, 2011·Nature Structural & Molecular Biology·Thomas SchalchLeemor Joshua-Tor
Nov 25, 2011·Methods in Molecular Biology·Bing TianAllan R Brasier
Apr 5, 2012·Nature Reviews. Genetics·Eric L Greer, Yang Shi
Jun 19, 2013·The EMBO Journal·Benjamin J AlperJanet F Partridge
Jan 23, 2014·Proceedings of the National Academy of Sciences of the United States of America·Canan KuscuLeemor Joshua-Tor
Jul 16, 2014·Molecular Cell·Jiamu DuSteven E Jacobsen
Dec 3, 2014·Biochimica Et Biophysica Acta·Maren Kirstin SchuhmacherAlbert Jeltsch
Apr 4, 2015·Science·Pauline N C B AudergonRobin C Allshire
Jan 26, 2016·Nature Chemical Biology·Manuel M MüllerTom W Muir

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