Allele-specific expression identified rs2509956 as a novel long-distance cis-regulatory SNP for SCGB1A1, an important gene for multiple pulmonary diseases
机构：[1]National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, People’s Republic of China[2]Department of Respiratory Critical Care Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China昆明医科大学附属第一医院[3]State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, People’s Republic of China[4]Provincial Demonstration Center for Experimental Biology Education, Shaanxi Normal University, Xi’an, People’s Republic of China
SCGB1A1 (secretoglobin family 1A member 1) is an important protein for multiple pulmonary diseases. especially asthma, chronic obstructive pulmonary disease, and lung cancer. One single-nucleotide polymorphism (SNP) at 5'-untranslated region of SCGB1A1, rs3741240. has been suggested to be associated with reduced protein expression and further asthma susceptibility. However, it was still unclear whether there were other cis-regulatory elements for SCGB1A1 that might further contribute to pulmonary diseases. Allele-specific expression (ASE) is a novel approach to identify the functional region in human genome. In the present study, we measured ASE on rs3741240 in lung tissues and observed a consistent excess of G allele over A (P < 10(-6)), which indicated that this SNP or the one(s) in linkage disequilibrium (LD) could regulate SCGB1A1 expression. By analyzing 1000 Genomes Project data for Chinese. one SNP locating similar to 10.2 kb away and downstream of SCGB1A1, rs2509956, was identified to be in strong Li) with rs3741240. Reporter gene assay confirmed that both SNPs could regulate gene expression in the lung cell. By chromosome conformation capture, it was verified that the region surrounding rs2509956 could interact with SCGB1A1 promoter region and act as an enhancer. Through chromatin immunoprecipitation and overexpression assay, the related transcription factor RELA (RELA proto-oncogene, NF-kB subunit) was recognized to bind the region spanning rs2509956. Our work identified a novel long-distance cis-regulatory SNP for SCGB1A1, which might contribute to multiple pulmonary diseases.
基金：
Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [GK201703031, GK201701005]; Yunnan Provincial Science and Technology Department [2017FE467-030]; High Level Talent Training Program in Yunnan [D-201662]; Kunming Medical University [2017FE467-030]
第一作者机构：[1]National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, People’s Republic of China
共同第一作者：
通讯作者：
通讯机构：[1]National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, People’s Republic of China[*1]College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi 710119, P.R. China
推荐引用方式(GB/T 7714)：
Li Xiu-Xiong,Peng Tao,Gao Jing,et al.Allele-specific expression identified rs2509956 as a novel long-distance cis-regulatory SNP for SCGB1A1, an important gene for multiple pulmonary diseases[J].AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY.2019,317(4):L456-L463.doi:10.1152/ajplung.00275.2018.
APA：
Li, Xiu-Xiong,Peng, Tao,Gao, Jing,Feng, Jia-Gang,Wu, Dan-Dan...&Sun, Chang.(2019).Allele-specific expression identified rs2509956 as a novel long-distance cis-regulatory SNP for SCGB1A1, an important gene for multiple pulmonary diseases.AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY,317,(4)
MLA：
Li, Xiu-Xiong,et al."Allele-specific expression identified rs2509956 as a novel long-distance cis-regulatory SNP for SCGB1A1, an important gene for multiple pulmonary diseases".AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 317..4(2019):L456-L463
