Functional role of G9a-induced histone methylation in small heterodimer partner-mediated transcriptional repression.
Site-specific modification of nucleosomal histones plays a central role in the formation of transcriptionally active and inactive chromatin structures. These modifications may serve as specific recognition motifs for chromatin proteins, which act as a signal for the adoption of the appropriate regulatory responses. Here, we show that the orphan nuclear receptor SHP (small heterodimer partner), a coregulator that inhibits the activity of several nuclear receptors, can associate with unmodified and lysine 9-methylated histone-3, but not with the acetylated protein. The naturally occurring SHP mutant (R213C), which exhibits decreased transrepression potential, interacts less avidly with K9-methylated histone 3. We demonstrate that SHP can functionally interact with histone deacetylase-1 and the G9a methyltransferase and that it is localized exclusively in nuclease-sensitive euchromatin. The results point to the involvement of a multistep mechanism in SHP-dependent transcriptional repression, which includes histone deacetylation, followed by H3-K9 methylation and stable association of SHP itself with chromatin.
Boulias
Konstantinos
K
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, PO Box 1527, Vassilika Vouton, 711 10 Herakleion, Crete, Greece.
Talianidis
Iannis
I
D000107:Acetylation; D000818:Animals; D002460:Cell Line; D022041:Euchromatin / Q000737:chemistry; D020868:Gene Silencing; D006655:Histone Deacetylases / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism* / Q000502:physiology; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D011496:Protein Methyltransferases; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000378:metabolism*; D012097:Repressor Proteins / Q000032:analysis / Q000378:metabolism*; D014158:Transcription, Genetic
D022041:Euchromatin; D006657:Histones; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; C099713:nuclear receptor subfamily 0, group B, member 2; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006655:Histone Deacetylases