دورية أكاديمية

ChIP-seq analysis found IL21R, a target gene of GTF2I-the susceptibility gene for primary biliary cholangitis in Chinese Han.

التفاصيل البيبلوغرافية
العنوان: ChIP-seq analysis found IL21R, a target gene of GTF2I-the susceptibility gene for primary biliary cholangitis in Chinese Han.
المؤلفون: Wu Z; Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China., Li H; Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China., Xu H; Department of Rheumatology and Clinical Immunology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China., Feng F; Department of Rheumatology and Clinical Immunology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China., Zhang F; Department of Rheumatology and Clinical Immunology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China., Zhang S; Department of Rheumatology and Clinical Immunology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. shulanpumch@126.com., Wang L; Department of Rheumatology and Clinical Immunology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. wangli2221@sina.com., Li Y; Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China. yongzhelipumch@126.com.
المصدر: Hepatology international [Hepatol Int] 2024 Apr; Vol. 18 (2), pp. 509-516. Date of Electronic Publication: 2023 Sep 15.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Country of Publication: United States NLM ID: 101304009 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1936-0541 (Electronic) Linking ISSN: 19360533 NLM ISO Abbreviation: Hepatol Int Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Springer
مواضيع طبية MeSH: Liver Cirrhosis, Biliary*/genetics , Transcription Factors, TFII*/genetics , Transcription Factors, TFIII*/genetics, Humans ; 5' Untranslated Regions ; China ; Chromatin Immunoprecipitation Sequencing ; Receptors, Interleukin-21/genetics
مستخلص: Aims: Aimed to identify a new susceptibility gene associated with primary biliary cholangitis (PBC) in Chinese Han and investigate the possible mechanism of that gene in PBC.
Methods: A total of 466 PBC and 694 healthy controls (HC) were included in our study, and genotyping GTF2I gene variants by Sequenom. CD19 + B cells were isolated for Chromatin immunoprecipitation sequencing (ChIP-seq). Additionally, MEME-ChIP was utilized to perform searches for known motifs and de novo motif discovery. The GTF2I ChIP-seq of hematopoietic cell line (K562) results were obtained from ENCODE (GSE176987, GSE177691). The Genomic HyperBrowser was used to determine overlap and hierarchal clustering between ours and ENCODE datasets.
Results: The frequency of the rs117026326 variant T allele was significantly higher in PBC patients than that in HC (20.26% compared with 13.89%, Pc = 1.09E-04). Furthermore, we observed an elevated proportion of GTF2I binding site located in the upstream and 5' UTR of genes in PBC in comparison with HC. Additionally, an in-depth analysis of IL21R region revealed that GTF2I might bind to the IL21R promoter to regulate the expression of the IL21R, with four peaks of GTF2I binding sites, including three increased binding sites in upstream, one increased binding site in 5' UTR. Motif analysis by MEME-ChIP uncovered five significant motifs. A significant overlap between our ChIP and GSE176987, GSE17769 were found by the Genomic HyperBroswer.
Conclusions: Our study confirmed that GTF2I was associated with PBC in Chinese Han. Furthermore, our gene function analysis indicated that IL21R may be the target gene regulated by GTF2I.
(© 2023. Asian Pacific Association for the Study of the Liver.)
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معلومات مُعتمدة: 81871302 the National Natural Science Foundation of China Grants; 81801631 the National Natural Science Foundation of China Grants; 2018YFE0207300 the National Key Research and Development Program of China; Z211100002521021 Beijing Municipal Science & Technology Commission; 2022-PUMCH-B-124 the National High Level Hospital Clinical Research Funding; 2022-PUMCH-A-007 the National High Level Hospital Clinical Research Funding
فهرسة مساهمة: Keywords: ChIP-seq; GTF2I; IL21R; PBC; Susceptibility gene
المشرفين على المادة: 0 (5' Untranslated Regions)
0 (GTF2I protein, human)
0 (Receptors, Interleukin-21)
0 (Transcription Factors, TFII)
0 (Transcription Factors, TFIII)
0 (IL21R protein, human)
تواريخ الأحداث: Date Created: 20230915 Date Completed: 20240415 Latest Revision: 20240508
رمز التحديث: 20240508
DOI: 10.1007/s12072-023-10586-x
PMID: 37713154
قاعدة البيانات: MEDLINE
الوصف
تدمد:1936-0541
DOI:10.1007/s12072-023-10586-x