title: Transcriptional regulation of heterogeneous nuclear ribonucleoprotein K gene expression.
abstract: Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is importantly involved in the regulation of development, DNA damage response, and several human diseases. The molecular mechanisms that control the expression of hnRNP K are largely unknown. In the present study, we investigated the detailed mechanism of the transcriptional regulation of human hnRNP K gene. Two activating and one repressive elements located in the proximal segment of the transcriptional initiation site were identified in hnRNP K gene. A 19 bp-region was responsible for the inhibitory activities of the repressor element. Twenty proteins were identified by DNA-affinity purification and mass spectrometry analyses as binding partners of the primary activating element in the hnRNP K promoter. Chromatin immunoprecipitation and EMSA analysis confirmed the binding of Sp1 with hnRNP K promoter. Sp1 enhanced the promoter activity, increased the expression of hnRNP K, and reduced the mRNA level of angiotensinogen, a gene known to be negatively regulated by hnRNP K. In summary, the current study characterized the promoter elements that regulate the transcription of human hnRNP K gene, identified 20 proteins that bind to the primary activating element of hnRNP K promoter, and demonstrated a functional effect of Sp1 on hnRNP K transcription.
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China; State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Liqing
authors.initials: L
authors.lastname: He
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Xue
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Entai
authors.initials: E
authors.lastname: Hou
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: zhangyqh@fmmu.edu.cn.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China. Electronic address: zmtian@mail.xjtu.edu.cn.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Tian
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D020218:Response Elements / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D020543:Proteome; D016329:Sp1 Transcription Factor
keywords: Gene expression; Promoter; Sp1; Transcription; hnRNP K