Crucial silencing factor contributing to the initiation of X inactivation mediated by Xist RNA that occurs during embryogenesis and in lymphoma (By similarity). Binds to DNA at special AT-rich sequences, the consensus SATB1-binding sequence (CSBS), at nuclear matrix- or scaffold-associated regions. Thought to recognize the sugar-phosphate structure of double-stranded DNA. Transcriptional repressor controlling nuclear and viral gene expression in a phosphorylated and acetylated status-dependent manner, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin-loop remodeling. Acts as a docking site for several chromatin remodeling enzymes (e.g. PML at the MHC-I locus) and also by recruiting corepressors (HDACs) or coactivators (HATs) directly to promoters and enhancers. Modulates genes that are essential in the maturation of the immune T-cell CD8SP from thymocytes. Required for the switching of fetal globin species, and beta- and gamma-globin genes regulation during erythroid differentiation. Plays a role in chromatin organization and nuclear architecture during apoptosis. Interacts with the unique region (UR) of cytomegalovirus (CMV). Alu-like motifs and SATB1-binding sites provide a unique chromatin context which seems preferentially targeted by the HIV-1 integration machinery. Moreover, HIV-1 Tat may overcome SATB1-mediated repression of IL2 and IL2RA (interleukin) in T-cells by binding to the same domain than HDAC1. Delineates specific epigenetic modifications at target gene loci, directly upregulating metastasis-associated genes while downregulating tumor-suppressor genes. Reprograms chromatin organization and the transcription profiles of breast tumors to promote growth and metastasis.
Expressed predominantly in thymus.
Belongs to the CUT homeobox family. Contains 2 CUT DNA-binding domains. Contains 1 homeobox DNA-binding domain.
Sumoylated. Sumoylation promotes cleavage by caspases. Phosphorylated by PKC. Acetylated by PCAF. Phosphorylated form interacts with HDAC1, but unphosphorylated form interacts with PCAF. DNA binding properties are activated by phosphorylation and inactivated by acetylation. In opposition, gene expression is down-regulated by phosphorylation but up-regulated by acetylation. Cleaved at Asp-254 by caspase-3 and caspase-6 during T-cell apoptosis in thymus and during B-cell stimulation. The cleaved forms can not dimerize and lose transcription regulation function because of impaired DNA and chromatin association.
Nucleus matrix. Nucleus > PML body. Organized into a cage-like network anchoring loops of heterochromatin and tethering specialized DNA sequences. When sumoylated, localized in promyelocytic leukemia nuclear bodies.