Comprehensive meta-analysis of Signal Transducers and Activators of Transcription (STAT) genomic binding patterns discerns cell-specific cis-regulatory modules

BMC Genomics

Research Article

Keunsoo Kang¹  Gertraud W Robinson¹  Lothar Hennighausen² 

[1] Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Drive, 20892-0822, Bethesda, MD, USA;Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Drive, 20892-0822, Bethesda, MD, USA;National Department of Nanobiomedical Science and WCU Research Center of Nanobiomedical Science, Dankook University, 330-714, Cheonan, Chungnam, Republic of Korea;

关键词: STAT;    GAS motif;    Meta-analysis;    ChIP-seq;    Cis;    CRM;   

DOI  :  10.1186/1471-2164-14-4

 received in 2012-08-23, accepted in 2013-01-01,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundCytokine-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.ResultsWe 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, ~15% of STAT5 binding sites in mouse female liver are shared by other STATs in different cell types while in T cells ~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.ConclusionsOur 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.

【 授权许可】

CC BY   
© Kang et al.; licensee BioMed Central Ltd. 2013