Acetylation-dependent interaction of SATB1 and CtBP1 mediates transcriptional repression by SATB1.
Special AT-rich binding protein 1 (SATB1) acts as a global regulator of gene expression by recruiting various corepressor or coactivator complexes, thereby establishing a unique chromatin structure at its genomic targets in a context-dependent manner. Although SATB1 acts predominantly as a repressor via recruitment of histone deacetylase 1 (HDAC1) complexes, the precise mechanism of global repression is not clear. Here we report that SATB1 and C-terminal binding protein 1 (CtBP1) form a repressor complex in vivo. The interaction occurs via the CtBP1 interaction consensus motif PVPLS within the PDZ-like domain of SATB1. The acetylation of SATB1 upon LiCl and ionomycin treatments disrupts its association with CtBP1, resulting in enhanced target gene expression. Chromatin immunoprecipitation analysis indicated that the occupancy of CtBP1 and HDAC1 is gradually decreased and the occupancy of PCAF is elevated at the SATB1 binding sites within the human interleukin-2 and mouse c-Myc promoters. Moreover, gene expression profiling studies using cells in which expression of SATB1 and CtBP1 was silenced indicated commonly targeted genes that may be coordinately repressed by the SATB1-CtBP1 complex. Collectively, these results provide a mechanistic insight into the role of SATB1-CtBP1 interaction in the repression and derepression of SATB1 target genes during Wnt signaling in T cells.
Purbey
Prabhat Kumar
PK
National Centre for Cell Science, NCCS Complex, Ganeshkhind, Pune 411007, India.
Singh
Sunita
S
Notani
Dimple
D
Kumar
P Pavan
PP
Limaye
Amita S
AS
Galande
Sanjeev
S
D000107:Acetylation; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D019169:Jurkat Cells; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000378:metabolism
D004268:DNA-Binding Proteins; D036961:Matrix Attachment Region Binding Proteins; D012097:Repressor Proteins; C076189:SATB1 protein, human; D051153:Wnt Proteins; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein