Genome-wide Analysis of STAT3-Mediated Transcription during Early Human Th17 Cell Differentiation

Cell Reports

Kari Nousiainen¹  Antti Larjo¹  Tarmo Äijo¹  Cisca Wijmenga²  Barbara Hrdlickova²  Isis Ricaño-Ponce²  Vinod Kumar²  Essi Laajala³  Harri Lähdesmäki³  Riitta Lahesmaa³  Kartiek Kanduri³  Soile Tuomela³  Zhi Chen³  Verna Salo³  Subhash K. Tripathi³ 

[1] Department of Computer Science, Aalto University, 02150 Espoo, Finland;Department of Genetics, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, the Netherlands;Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, 20500 Turku, Finland;

关键词: human;    Th17 cell differentiation;    STAT3;    ChIP-seq;    SNP;   

DOI  :  10.1016/j.celrep.2017.05.013

来源: DOAJ

【 摘 要 】

The development of therapeutic strategies to combat immune-associated diseases requires the molecular mechanisms of human Th17 cell differentiation to be fully identified and understood. To investigate transcriptional control of Th17 cell differentiation, we used primary human CD4+ T cells in small interfering RNA (siRNA)-mediated gene silencing and chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq) to identify both the early direct and indirect targets of STAT3. The integrated dataset presented in this study confirms that STAT3 is critical for transcriptional regulation of early human Th17 cell differentiation. Additionally, we found that a number of SNPs from loci associated with immune-mediated disorders were located at sites where STAT3 binds to induce Th17 cell specification. Importantly, introduction of such SNPs alters STAT3 binding in DNA affinity precipitation assays. Overall, our study provides important insights for modulating Th17-mediated pathogenic immune responses in humans.

【 授权许可】

Unknown