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

被引：92

作者：

Tripathi, Subhash K. ^{[1
,2
,3
,7
]}

Chen, Zhi ^{[1
,2
]}

Larjo, Antti ^{[4
,5
]}

Kanduri, Kartiek ^{[1
,2
,4
]}

Nousiainen, Kari ^{[4
]}

Aijo, Tarmo ^{[4
]}

Ricano-Ponce, Isis ^{[6
]}

Hrdlickova, Barbara ^{[6
]}

Tuomela, Soile ^{[1
,2
]}

Laajala, Essi ^{[1
,2
]}

Salo, Verna ^{[1
,2
]}

Kumar, Vinod ^{[6
]}

Wijmenga, Cisca ^{[6
]}

Lahdesmaki, Harri ^{[1
,2
,4
]}

Lahesmaa, Riitta ^{[1
,2
]}

机构：

[1] Univ Turku, Turku Ctr Biotechnol, Turku 20500, Finland

[2] Abo Akad Univ, Turku 20500, Finland

[3] Natl Doctoral Programme Informat & Struct Biol, Turku 20520, Finland

[4] Aalto Univ, Dept Comp Sci, Espoo 02150, Finland

[5] Finnish Red Cross Blood Serv, Helsinki 00310, Finland

[6] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 GZ Groningen, Netherlands

[7] Turku Doctoral Programme Mol Med TuDMM, Turku 20014, Finland

来源：

CELL REPORTS | 2017年 / 19卷 / 09期

基金：

芬兰科学院;

关键词：

HYPER-IGE SYNDROME; HELPER T-CELLS; WEB-BASED TOOL; AUTOIMMUNE-DISEASE; T-H-17; CELLS; TGF-BETA; STAT3; IDENTIFICATION; GENERATION; MUTATIONS;

D O I：

10.1016/j.celrep.2017.05.013

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

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.

引用

页码：1888 / 1901

页数：14

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