期刊
BMC GENOMICS
卷 14, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1471-2164-14-4
关键词
STAT; GAS motif; Meta-analysis; ChIP-seq; Cis-regulatory module; CRM
资金
- Intramural Research Programs (IRP) of NIDDK at the National Institutes of Health (NIH), USA
- World Class University Program, Ministry of Education, Science and Technology, through the National Research Foundation of Korea, South Korea [R31-10069]
- WCU Research Center, Dankook University
Background: Cytokine-activated transcription factors from the STAT (Signal Transducers and Activators of Transcription) family control common and context-specific genetic programs. It is not clear to what extent cell-specific features determine the binding capacity of seven STAT members and to what degree they share genetic targets. Molecular insight into the biology of STATs was gained from a meta-analysis of 29 available ChIP-seq data sets covering genome-wide occupancy of STATs 1, 3, 4, 5A, 5B and 6 in several cell types. Results: We determined that the genomic binding capacity of STATs is primarily defined by the cell type and to a lesser extent by individual family members. For example, the overlap of shared binding sites between STATs 3 and 5 in T cells is greater than that between STAT5 in T cells and non-T cells. Even for the top 1,000 highly enriched STAT binding sites, similar to 15% of STAT5 binding sites in mouse female liver are shared by other STATs in different cell types while in T cells similar to 90% of STAT5 binding sites are co-occupied by STAT3, STAT4 and STAT6. In addition, we identified 116 cis-regulatory modules (CRM), which are recognized by all STAT members across cell types defining a common JAK-STAT signature. Lastly, in liver STAT5 binding significantly coincides with binding of the cell-specific transcription factors HNF4A, FOXA1 and FOXA2 and is associated with cell-type specific gene transcription. Conclusions: Our results suggest that genomic binding of STATs is primarily determined by the cell type and further specificity is achieved in part by juxtaposed binding of cell-specific transcription factors.
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