PMID- 24497979
OWN - NLM
STAT- MEDLINE
DCOM- 20141222
LR  - 20220129
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 1
DP  - 2014
TI  - Identification of STAT5A and STAT5B target genes in human T cells.
PG  - e86790
LID - 10.1371/journal.pone.0086790 [doi]
LID - e86790
AB  - 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.
FAU - Kanai, Takahiro
AU  - Kanai T
AD  - Division of Immunology and Allergy, Department of Pediatrics, School of Medicine, 
      Stanford University, Stanford, California, United States of America.
FAU - Seki, Scott
AU  - Seki S
AD  - Division of Immunology and Allergy, Department of Pediatrics, School of Medicine, 
      Stanford University, Stanford, California, United States of America.
FAU - Jenks, Jennifer A
AU  - Jenks JA
AD  - Division of Immunology and Allergy, Department of Pediatrics, School of Medicine, 
      Stanford University, Stanford, California, United States of America.
FAU - Kohli, Arunima
AU  - Kohli A
AD  - Division of Immunology and Allergy, Department of Pediatrics, School of Medicine, 
      Stanford University, Stanford, California, United States of America.
FAU - Kawli, Trupti
AU  - Kawli T
AD  - Department of Genetics, School of Medicine, Stanford University, Stanford, 
      California, United States of America.
FAU - Martin, Dorrelyn Patacsil
AU  - Martin DP
AD  - Department of Genetics, School of Medicine, Stanford University, Stanford, 
      California, United States of America.
FAU - Snyder, Michael
AU  - Snyder M
AD  - Department of Genetics, School of Medicine, Stanford University, Stanford, 
      California, United States of America.
FAU - Bacchetta, Rosa
AU  - Bacchetta R
AD  - 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.
FAU - Nadeau, Kari C
AU  - Nadeau KC
AD  - Division of Immunology and Allergy, Department of Pediatrics, School of Medicine, 
      Stanford University, Stanford, California, United States of America.
LA  - eng
GR  - TGT11A04/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140130
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (STAT5A protein, human)
RN  - 0 (STAT5B protein, human)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Base Sequence
MH  - Binding Sites
MH  - CD4-Positive T-Lymphocytes/*physiology
MH  - Cells, Cultured
MH  - Consensus Sequence
MH  - Humans
MH  - Protein Multimerization
MH  - STAT5 Transcription Factor/*physiology
MH  - Transcriptional Activation
MH  - Transcriptome
MH  - Tumor Suppressor Proteins/*physiology
PMC - PMC3907443
COIS- Competing Interests: The authors declare no conflict of interest.
EDAT- 2014/02/06 06:00
MHDA- 2014/12/23 06:00
PMCR- 2014/01/30
CRDT- 2014/02/06 06:00
PHST- 2013/08/15 00:00 [received]
PHST- 2013/12/13 00:00 [accepted]
PHST- 2014/02/06 06:00 [entrez]
PHST- 2014/02/06 06:00 [pubmed]
PHST- 2014/12/23 06:00 [medline]
PHST- 2014/01/30 00:00 [pmc-release]
AID - PONE-D-13-33933 [pii]
AID - 10.1371/journal.pone.0086790 [doi]
PST - epublish
SO  - PLoS One. 2014 Jan 30;9(1):e86790. doi: 10.1371/journal.pone.0086790. eCollection 
      2014.