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

JD Alvarez, DH Yasui, H Niida, T Joh… - Genes & …, 2000 - genesdev.cshlp.org
JD Alvarez, DH Yasui, H Niida, T Joh, DY Loh, T Kohwi-Shigematsu
Genes & development, 2000genesdev.cshlp.org
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 …
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 CD3CD4CD8 triple negative (TN) thymocytes were greatly reduced in number, and thymocyte development was blocked mainly at the DP stage. The few peripheral CD4+ 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-2Rα andIL-7Rα genes were ectopically transcribed in CD4+CD8+ 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.
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