BCL11A-dependent recruitment of SIRT1 to a promoter template in mammalian cells results in histone deacetylation and transcriptional repression.
The B cell leukemia 11A protein (BCL11A/Evi9/CTIP1) has been implicated in hematopoietic cell development and malignancies. BCL11A is a transcriptional repressor that binds directly to a GC-rich motif and is also recruited to a promoter template via interaction with the orphan nuclear receptor, chicken ovalbumin upstream promoter transcription factor II. In both cases, BCL11A-mediated transcriptional repression is only minimally reversed by trichostatin A, suggesting the possible lack of involvement of class I or II histone deacetylases. Nonetheless, chromatin immunoprecipitation assays revealed that expression of BCL11A in mammalian cells resulted in deacetylation of histones H3 and/or H4 that were associated with the promoter region of a reporter gene. BCL11A-mediated transcriptional repression, as well as deacetylation of histone H3/H4 in BCL11A-transfected cells, was partially reversed by nicotinamide, an inhibitor of class III histone deacetylases such as SIRT1. SIRT1 was found to interact directly with BCL11A and was recruited to the promoter template in a BCL11A-dependent manner leading to transcriptional repression. These findings define a role for SIRT1 in transcriptional repression mediated by BCL11A in mammalian cells.
Senawong
Thanaset
T
Program in Molecular and Cellular Biology, Oregon State University, Corvallis, OR 97331, USA.
Peterson
Valerie J
VJ
Leid
Mark
M
D020816:Amino Acid Motifs; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D017353:Gene Deletion; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000737:chemistry*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D047468:Immunoprecipitation; D008957:Models, Genetic; D009536:Niacinamide / Q000737:chemistry / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins; D056564:Sirtuin 1; D037761:Sirtuins / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
C486563:BCL11A protein, human; D002352:Carrier Proteins; D006657:Histones; D006877:Hydroxamic Acids; D009687:Nuclear Proteins; D012097:Repressor Proteins; D009536:Niacinamide; C012589:trichostatin A; D005982:Glutathione Transferase; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D006655:Histone Deacetylases