SUMO modification is involved in the maintenance of heterochromatin stability in fission yeast.
Several studies have suggested that SUMO may participate in the regulation of heterochromatin, but direct evidence is lacking. Here, we present a direct link between sumoylation and heterochromatin stability. SUMO deletion impaired silencing at heterochromatic regions and induced histone H3 Lys4 methylation, a hallmark of active chromatin in fission yeast. Our findings showed that the SUMO-conjugating enzyme Hus5/Ubc9 interacted with the conserved heterochromatin proteins Swi6, Chp2 (a paralog of Swi6), and Clr4 (H3 Lys9 methyltransferase). Moreover, chromatin immunoprecipitation (ChIP) revealed that Hus5 was highly enriched in heterochromatic regions in a heterochromatin-dependent manner, suggesting a direct role of Hus5 in heterochromatin formation. We also found that Swi6, Chp2, and Clr4 themselves can be sumoylated in vivo and defective sumoylation of Swi6 or Chp2 compromised silencing. These results indicate that Hus5 associates with heterochromatin through interactions with heterochromatin proteins and modifies substrates whose sumoylations are required for heterochromatin stability, including heterochromatin proteins themselves.
Shin
Jin A
JA
Research Institute, National Cancer Center, Goyang, Gyeonggi 411-764, Republic of Korea.
Choi
Eun Shik
ES
Kim
Hyun Soo
HS
Ho
Jenny C Y
JC
Watts
Felicity Z
FZ
Park
Sang Dai
SD
Jang
Yeun Kyu
YK
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D043171:Chromosomal Instability; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D006570:Heterochromatin / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D029702:Schizosaccharomyces pombe Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; C465958:Swi6 protein, S pombe; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C112744:clr4 protein, S pombe; D044763:Ubiquitin-Conjugating Enzymes; C093855:HUS5 protein, S pombe