PMID- 20943203 OWN - NLM STAT- MEDLINE DCOM- 20110429 LR - 20211203 IS - 1872-8057 (Electronic) IS - 0303-7207 (Linking) VI - 332 IP - 1-2 DP - 2011 Jan 30 TI - Estrogen regulation of human with-no-lysine (K) kinase-4 gene expression involves AP-1 transcription factor. PG - 140-8 LID - 10.1016/j.mce.2010.10.006 [doi] AB - With-no-lysine (K) kinase-4 (WNK4) is a serine/threonine protein kinase and plays a crucial role in the regulation of blood pressure and electrolyte homeostasis. Whether or not estrogen, an important regulator of physiologic functions, modulates human WNK4 (hWNK4) gene expression is unknown. In the current study, real-time PCR assay showed that 17beta-estradiol (E(2)) with estrogen receptor alpha (ERalpha) suppressed the level of hWNK4 mRNA in cultured human embryo kidney 293 cells (HEK293). Luciferase activity analysis of the truncated hWNK4 promoters indicated that a regulatory region from -216 to -202 is essential for the basal transcriptional activity and response to E(2)/ERalpha. Using an electrophoresis mobility shift assay and a chromatin immunoprecipitation assay, we identified an activator protein-1 (AP-1) element at position -215/-205, to which AP-1 binding was enhanced by E(2)/ERalpha. Accordingly, AP-1 protein was increased by E(2)/ERalpha using Western blot analysis. Moreover, re-chromatin-immunoprecipitation and co-immunoprecipitation assays showed a direct interaction between ERalpha and AP-1 in HEK293 cells. In summary, these data document that E(2)/ERalpha regulates hWNK4 expression partly through AP-1 binding to the hWNK4 promoter. CI - Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved. FAU - Zhang, Yuanyuan AU - Zhang Y AD - Department of Medical Genetics, China Medical University, Shenyang, Liaoning, China. FAU - Li, Chunyi AU - Li C FAU - Li, Wei AU - Li W FAU - Zhao, Yanyan AU - Zhao Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101011 PL - Ireland TA - Mol Cell Endocrinol JT - Molecular and cellular endocrinology JID - 7500844 RN - 0 (Estrogen Receptor alpha) RN - 0 (Transcription Factor AP-1) RN - 4TI98Z838E (Estradiol) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (WNK4 protein, human) SB - IM MH - Base Sequence MH - Estradiol/*metabolism MH - Estrogen Receptor alpha/genetics/metabolism MH - *Gene Expression MH - HEK293 Cells MH - Humans MH - Molecular Sequence Data MH - Promoter Regions, Genetic MH - Protein Serine-Threonine Kinases/*genetics/metabolism MH - Transcription Factor AP-1/genetics/*metabolism MH - Transcription, Genetic EDAT- 2010/10/15 06:00 MHDA- 2011/04/30 06:00 CRDT- 2010/10/15 06:00 PHST- 2010/06/29 00:00 [received] PHST- 2010/09/14 00:00 [revised] PHST- 2010/10/05 00:00 [accepted] PHST- 2010/10/15 06:00 [entrez] PHST- 2010/10/15 06:00 [pubmed] PHST- 2011/04/30 06:00 [medline] AID - S0303-7207(10)00494-6 [pii] AID - 10.1016/j.mce.2010.10.006 [doi] PST - ppublish SO - Mol Cell Endocrinol. 2011 Jan 30;332(1-2):140-8. doi: 10.1016/j.mce.2010.10.006. Epub 2010 Oct 11.