The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development
SATB1 is expressed primarily in thymocytes and can act as a transcriptional repressor. SATB1 binds in vivo to the matrix attachment regions (MARs) of DNA, which are implicated in the loop domain organization of chromatin. The role of MAR-binding proteins in specific cell lineages is unknown. We generated SATB1-null mice to determine how SATB1 functions in the T-cell lineage. SATB1-null mice are small in size, have disproportionately small thymi and spleens, and die at 3 weeks of age. At the cellular level, multiple defects in T-cell development were observed. Immature CD3-CD4-CD8 triple negative (TN) thymocytes were greatly reduced in number, and thymocyte development was blocked mainly at the DP stage. The few peripheral CD4{sup +} single positive (SP) cells underwent apoptosis and failed to proliferate in response to activating stimuli. At the molecular level, among 589 genes examined, at least 2% of genes including a proto-oncogene, cytokine receptor genes, and apoptosis-related genes were derepressed at inappropriate stages of T-cell development in SATB1-null mice. For example, IL-2R{alpha} and IL-7R{alpha} genes were ectopically transcribed in CD4{sup 4+}-CD{sup 8+} double positive (DP) thymocytes. SATB1 appears to orchestrate the temporal and spatial expression of genes during T-cell development, thereby ensuring the proper development of this lineage. Our data provide the first evidence that MAR-binding proteins can act as global regulators of cell function in specific cell lineages.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- National Institutes of Health (US)
- DOE Contract Number:
- AC03-76SF00098
- OSTI ID:
- 771795
- Report Number(s):
- LBNL-45216; R&D Project: 862516; TRN: AH200104%%342
- Journal Information:
- Genes & Development, Vol. 14, Issue 5; Other Information: PBD: 24 Feb 2000
- Country of Publication:
- United States
- Language:
- English
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