NF-κB inhibits transcription of the H+-K+-ATPase α2-subunit gene:: role of histone deacetylases

被引:61
|
作者
Zhang, WZ
Kone, BC
机构
[1] Univ Texas, Sch Med, Dept Internal Med, Houston, TX 77030 USA
[2] Univ Texas, Sch Med, Dept Integrat Biol Pharmacol & Physiol, Houston, TX 77030 USA
关键词
kidney; colon; trichostatin A; promoter;
D O I
10.1152/ajprenal.00156.2002
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The H+-K+-ATPase alpha(2) (HKalpha(2)) gene plays a central role in potassium homeostasis, yet little is known about its transcriptional control. We recently demonstrated that the proximal promoter confers basal transcriptional activity in mouse inner medullary collecting duct 3 cells. We sought to determine whether the kappaB DNA binding element at -104 to -94 influences basal HKalpha(2) gene transcription in these cells. Recombinant NF-kappaB p50 footprinted the region -116/-94 in vitro. Gel shift and supershift analysis revealed NF-kappaB p50- and p65-containing DNA-protein complexes in nuclear extracts of mouse inner medullary collecting duct 3 cells. A promoter-luciferase construct with a mutated -104/-94 NF-kappaB element exhibited higher activity than the wild-type promoter in transfection assays. Overexpression of NF-kappaB p50, p65, or their combination transrepressed the HKalpha(2) promoter. The histone deacetylase (HDAC) inhibitor trichostatin A partially reversed NF-kappaB-mediated trans-repression of the HKalpha(2) promoter. HDAC6 overexpression inhibited HKalpha(2) promoter activity, and HDAC6 coimmunoprecipitated with NF-kappaB p50 and p65. These results suggest that HDAC6, recruited to the DNA protein complex, acts with NF-kappaB to suppress HKalpha(2) transcription and identify NF-kappaB p50 and p65 as novel binding partners for HDAC6.
引用
收藏
页码:F904 / F911
页数:8
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