Abstract
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.
SUPPLEMENTAL MATERIAL
Supplemental material for this article may be found at http://mcb.asm.org/ .
ACKNOWLEDGMENTS
We thank G. Chinnadurai and B. L. Firestein for CtBP1 constructs and S. Schreiber for the FLAG-HDAC1 construct. We thank M. C. Raja and V. Madavan from Genotypic Technology, Bangalore, India, for help with microarray data analysis. We also thank Ranveer Jayani, Nitin Sonawane, and R. L. Praveena for technical assistance.
This work was supported by grants from the Department of Biotechnology, Government of India, and the Wellcome Trust, United Kingdom. P.K.P., P.P.K., D.N., and S.S. are supported by fellowships from the Council of Scientific and Industrial Research, India. A.L. is supported by a fellowship from the University Grants Commission, India. S.G. is an international senior research fellow of the Wellcome Trust.