Genome-wide Analysis of STAT3-Mediated Transcription during Early Human Th17 Cell Differentiation
Tripathi Subhash K; Salo Verna; Lahdesmaki Harri; Hrdlickova Barbara; Kanduri Kartiek; Tuomela Soile; Chen Zhi; Lahesmaa Riitta; Kumar Vinod; Larjo Antti; Wijmenga Cisca; Ricano-Ponce Isis; Aijo Tarmo; Laajala Essi; Nousiainen Kari
https://urn.fi/URN:NBN:fi-fe2021042716983
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]