A1 Refereed original research article in a scientific journal
Genome-wide Analysis of STAT3-Mediated Transcription during Early Human Th17 Cell Differentiation
Authors: Tripathi Subhash K, Chen Zhi, Larjo Antti, Kanduri Kartiek, Nousiainen Kari, Aijo Tarmo, Ricano-Ponce Isis, Hrdlickova Barbara, Tuomela Soile, Laajala Essi, Salo Verna, Kumar Vinod, Wijmenga Cisca, Lahdesmaki Harri, Lahesmaa Riitta
Publisher: CellPress
Publication year: 2017
Journal: Cell Reports
Journal acronym: Cell Rep
Volume: 19
Issue: 9
First page : 1888
Last page: 1901
Number of pages: 14
ISSN: 2211-1247
DOI: https://doi.org/10.1016/j.celrep.2017.05.013(external)
Self-archived copy’s web address: https://research.utu.fi/converis/portal/Publication/25216932(external)
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.
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