Identification of STAT5A and STAT5B target genes in human T cells.
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 mic...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0086790&type=printable |
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| author | Takahiro Kanai Scott Seki Jennifer A Jenks Arunima Kohli Trupti Kawli Dorrelyn Patacsil Martin Michael Snyder Rosa Bacchetta Kari C Nadeau |
| author_facet | Takahiro Kanai Scott Seki Jennifer A Jenks Arunima Kohli Trupti Kawli Dorrelyn Patacsil Martin Michael Snyder Rosa Bacchetta Kari C Nadeau |
| author_sort | Takahiro Kanai |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-df6e7147cc9a4641b16f53d323cf0e7b |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-df6e7147cc9a4641b16f53d323cf0e7b2025-08-20T02:22:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8679010.1371/journal.pone.0086790Identification of STAT5A and STAT5B target genes in human T cells.Takahiro KanaiScott SekiJennifer A JenksArunima KohliTrupti KawliDorrelyn Patacsil MartinMichael SnyderRosa BacchettaKari C NadeauSignal 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0086790&type=printable |
| spellingShingle | Takahiro Kanai Scott Seki Jennifer A Jenks Arunima Kohli Trupti Kawli Dorrelyn Patacsil Martin Michael Snyder Rosa Bacchetta Kari C Nadeau Identification of STAT5A and STAT5B target genes in human T cells. PLoS ONE |
| title | Identification of STAT5A and STAT5B target genes in human T cells. |
| title_full | Identification of STAT5A and STAT5B target genes in human T cells. |
| title_fullStr | Identification of STAT5A and STAT5B target genes in human T cells. |
| title_full_unstemmed | Identification of STAT5A and STAT5B target genes in human T cells. |
| title_short | Identification of STAT5A and STAT5B target genes in human T cells. |
| title_sort | identification of stat5a and stat5b target genes in human t cells |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0086790&type=printable |
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