SATB1
Description
The SATB1 (SATB homeobox 1) is a protein-coding gene located on chromosome 3.
SATB1 (special AT-rich sequence-binding protein-1) is a protein which in humans is encoded by the SATB1 gene. It is a dimeric/tetrameric transcription factor with multiple DNA binding domains (CUT1, CUT2 and a Homeobox domain). SATB1 specifically binds to AT-rich DNA sequences with high unwinding propensity called base unpairing regions (BURs), containing matrix attachment regions (MARs).
== Function == SATB1 is as a key factor for regulating spatial genome organization and subsequently integrating higher-order chromatin architecture with gene regulation. By binding to MARs and tethering these to the nuclear matrix, SATB1 creates chromatin loops. By changing the chromatin-loop architecture SATB1 is able to change gene transcription. The majority of SATB1 binding sites in the DNA are occupied by CTCF as well, another important chromatin organizer.
=== Immune system === SATB1 has a multitude of roles in the development of T cells. SATB1 plays a role in controlling expression of lineage-specific factors during T cell development, including ThPOK, Runx3, CD4, CD8, and Treg factor Foxp3. SATB1-deficient thymocytes enter inappropriate T lineages and fail to generate the NKT and Treg subsets.
SATB1 is a crucial silencing factor involved in the initiation of X chromosome inactivation, a process mediated by Xist RNA that occurs during embryonic development and in lymphoma. It binds to specific AT-rich DNA sequences known as the consensus SATB1-binding sequence (CSBS) located at nuclear matrix- or scaffold-associated regions. SATB1 is thought to recognize the sugar-phosphate structure of double-stranded DNA. As a transcriptional repressor, it controls nuclear and viral gene expression in a manner dependent on its phosphorylation and acetylation status. SATB1 binds to matrix attachment regions (MARs) of DNA, inducing local chromatin loop remodeling. It acts as a docking site for several chromatin remodeling enzymes, such as PML at the MHC-I locus, and recruits corepressors (HDACs) or coactivators (HATs) directly to promoters and enhancers. SATB1 modulates genes crucial for the maturation of immune T-cell CD8SP from thymocytes and is required for the switching of fetal globin species and the regulation of beta- and gamma-globin genes during erythroid differentiation. It plays a role in chromatin organization and nuclear architecture during apoptosis. SATB1 interacts with the unique region (UR) of cytomegalovirus (CMV). Alu-like motifs and SATB1-binding sites create a unique chromatin context that appears to be preferentially targeted by the HIV-1 integration machinery. Moreover, HIV-1 Tat can overcome SATB1-mediated repression of IL2 and IL2RA (interleukin) in T-cells by binding to the same domain as HDAC1. SATB1 delineates specific epigenetic modifications at target gene loci, directly up-regulating metastasis-associated genes while down-regulating tumor-suppressor genes. It reprograms chromatin organization and the transcription profiles of breast tumors to promote growth and metastasis. SATB1 promotes neuronal differentiation of neural stem/progenitor cells in the adult subventricular zone, possibly by positively regulating the expression of NEUROD1. SATB1 interacts with CUX1 via DNA-binding domains, and this interaction inhibits the attachment of both proteins to DNA. It forms homodimers and is part of the nuclear protein complex gamma-globin promoter and enhancer binding factor (gamma-PE) composed of at least SATB1 and HOXB2. When not acetylated, interaction with CtBP1 stabilizes attachment to DNA and promotes transcription repression. SATB1 interacts with PCAF, sumoylated PML, and HDAC1 via the ULD domain. It also interacts with DYNLT3, POLR2J2, and binds to EP300. SATB1 interacts with HIV-1 Tat via the ULD domain.
SATB1 is also known as DEFDA, DHDBV, KTZSL.
