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PLoS One. 2014 Jan 30;9(1):e86790. doi: 10.1371/journal.pone.0086790. eCollection 2014.

Identification of STAT5A and STAT5B target genes in human T cells.

Author information

1
Division of Immunology and Allergy, Department of Pediatrics, School of Medicine, Stanford University, Stanford, California, United States of America.
2
Department of Genetics, School of Medicine, Stanford University, Stanford, California, United States of America.
3
Division of Immunology and Allergy, Department of Pediatrics, School of Medicine, Stanford University, Stanford, California, United States of America ; San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), San Raffaele Scientific Institute, Milan, Italy.

Abstract

Signal transducer and activator of transcription (STAT) comprises a family of universal transcription factors that help cells sense and respond to environmental signals. STAT5 refers to two highly related proteins, STAT5A and STAT5B, with critical function: their complete deficiency is lethal in mice; in humans, STAT5B deficiency alone leads to endocrine and immunological problems, while STAT5A deficiency has not been reported. STAT5A and STAT5B show peptide sequence similarities greater than 90%, but subtle structural differences suggest possible non-redundant roles in gene regulation. However, these roles remain unclear in humans. We applied chromatin immunoprecipitation followed by DNA sequencing using human CD4(+) T cells to detect candidate genes regulated by STAT5A and/or STAT5B, and quantitative-PCR in STAT5A or STAT5B knock-down (KD) human CD4(+) T cells to validate the findings. Our data show STAT5A and STAT5B play redundant roles in cell proliferation and apoptosis via SGK1 interaction. Interestingly, we found a novel, unique role for STAT5A in binding to genes involved in neural development and function (NDRG1, DNAJC6, and SSH2), while STAT5B appears to play a distinct role in T cell development and function via DOCK8, SNX9, FOXP3 and IL2RA binding. Our results also suggest that one or more co-activators for STAT5A and/or STAT5B may play important roles in establishing different binding abilities and gene regulation behaviors. The new identification of these genes regulated by STAT5A and/or STAT5B has major implications for understanding the pathophysiology of cancer progression, neural disorders, and immune abnormalities.

PMID:
24497979
PMCID:
PMC3907443
DOI:
10.1371/journal.pone.0086790
[Indexed for MEDLINE]
Free PMC Article

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