The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development

Journal Article · Thu Feb 24 04:00:00 EST 2000 · Genes & Development

OSTI ID:771795

Alvarez, John D ^[1]; Yasui, Dag H; Niida, Hiroyuki; Joh, Tadashi; Loh, Dennis Y; Kowhi-Shigematsu, Terumi

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1. LBNL Library

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., CA (US)
• Sponsoring Organization: National Institutes of Health (US)
• DOE Contract Number: AC03-76SF00098
• OSTI ID: 771795
• Report Number(s): LBNL--45216
• Journal Information: Genes & Development, Journal Name: Genes & Development Journal Issue: 5 Vol. 14
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
APOPTOSIS
CHROMATIN
DEFECTS
DNA
GENES
IN VIVO
LYMPHOKINES
MICE
PROTEINS
THYMOCYTES