Medical College of Wisconsin
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Transcriptional regulation of heterogeneous nuclear ribonucleoprotein K gene expression. Biochimie 2015 Feb;109:27-35

Date

12/17/2014

Pubmed ID

25497182

Pubmed Central ID

PMC4414404

DOI

10.1016/j.biochi.2014.12.002

Scopus ID

2-s2.0-84919629421 (requires institutional sign-in at Scopus site)   8 Citations

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.

Author List

He L, Xue X, Wang Z, Hou E, Liu Y, Liang M, Zhang Y, Tian Z



MESH terms used to index this publication - Major topics in bold

Base Sequence
Binding Sites
Blotting, Western
Cell Line
Chromatin Immunoprecipitation
Electrophoretic Mobility Shift Assay
Gene Expression Regulation
HEK293 Cells
Heterogeneous-Nuclear Ribonucleoprotein K
Humans
MCF-7 Cells
Molecular Sequence Data
Promoter Regions, Genetic
Protein Binding
Proteome
Proteomics
Response Elements
Reverse Transcriptase Polymerase Chain Reaction
Sp1 Transcription Factor
Spectrometry, Mass, Electrospray Ionization