Dot1a-AF9 complex mediates histone H3 Lys-79 hypermethylation and repression of ENaCalpha in an aldosterone-sensitive manner.

The Journal of Biological Chemistry
Wenzheng ZhangBruce C Kone

Abstract

Aldosterone is a major regulator of epithelial Na(+) absorption and acts in large part through induction of the epithelial Na(+) channel (ENaC) gene in the renal collecting duct. We previously identified Dot1a as an aldosterone early repressed gene and a repressor of ENaCalpha transcription through mediating histone H3 Lys-79 methylation associated with the ENaCalpha promoter. Here, we report a novel aldosterone-signaling network involving AF9, Dot1a, and ENaCalpha. AF9 and Dot1a interact in vitro and in vivo as evidenced in multiple assays and colocalize in the nuclei of mIMCD3 renal collecting duct cells. Overexpression of AF9 results in hypermethylation of histone H3 Lys-79 at the endogenous ENaCalpha promoter at most, but not all subregions examined, repression of endogenous ENaCalpha mRNA expression and acts synergistically with Dot1a to inhibit ENaCalpha promoter-luciferase constructs. In contrast, RNA interference-mediated knockdown of AF9 causes the opposite effects. Chromatin immunoprecipitation assays reveal that overexpressed FLAG-AF9, endogenous AF9, and Dot1a are each associated with the ENaCalpha promoter. Aldosterone negatively regulates AF9 expression at both mRNA and protein levels. Thus, Dot1a-AF9 modulates hi...Continue Reading

References

May 1, 1993·Japanese Journal of Cancer Research : Gann·S IidaR Ueda
Aug 1, 1996·The American Journal of Physiology·C AsherH Garty
Oct 29, 1997·Molecular and Cellular Biology·S MinkK H Klempnauer
Jun 5, 1998·The American Journal of Physiology·J B Stokes, R D Sigmund
Aug 4, 2001·Molecular and Cellular Biology·Y L YaoE Seto
Mar 7, 2002·American Journal of Physiology. Renal Physiology·James D Stockand
Mar 14, 2002·The Journal of Membrane Biology·D C EatonG Yue
May 1, 2002·The Journal of General Physiology·Diego Alvarez de la RosaCecilia M Canessa
May 25, 2002·Molecular and Cellular Biology·Suzanne D TurnerChristopher J Brandl
Jun 19, 2002·The Journal of Biological Chemistry·Jim DoverAli Shilatifard
Jun 28, 2002·Cell·Fred van LeeuwenDaniel E Gottschling
Sep 13, 2002·American Journal of Physiology. Cell Physiology·Jianliang ZhangJawaharlal M Patel
Oct 10, 2002·American Journal of Physiology. Renal Physiology·Wenzheng Zhang, Bruce C Kone
Feb 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Huck Hui NgKevin Struhl
May 29, 2003·American Journal of Physiology. Renal Physiology·Michelle L GumzBrian D Cain
Oct 24, 2003·The Biochemical Journal·Wenzheng ZhangBruce C Kone
Nov 7, 2003·Leukemia·F ErfurthP H Domer
Feb 12, 2004·American Journal of Physiology. Renal Physiology·Wenzheng ZhangBruce C Kone
Feb 3, 2005·Proceedings of the National Academy of Sciences of the United States of America·Andrei KuzmichevDanny Reinberg
Apr 27, 2005·Cell·Yuki OkadaYi Zhang
Oct 21, 2005·American Journal of Physiology. Cell Physiology·Wenzheng ZhangBruce C Kone
May 3, 2005·Reproductive Medicine and Biology·Masaaki Morisawa, Manabu Yoshida

❮ Previous
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Citations

May 1, 2010·The Protein Journal·Geunyeong ParkJa-Eun Kim
Jan 5, 2013·International Journal of Hematology·Ly P VuStephen D Nimer
Jul 25, 2013·Journal of Medicinal Chemistry·Justin L Anglin, Yongcheng Song
Mar 27, 2009·Leukemia·T Neff, S A Armstrong
Oct 25, 2007·Nature Reviews. Cancer·Andrei V Krivtsov, Scott A Armstrong
Dec 24, 2009·Nature Reviews. Cancer·Jianjun ChenJanet D Rowley
May 31, 2008·Nature Structural & Molecular Biology·Floor FrederiksFred van Leeuwen
Mar 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Nicole BüttnerTanja Vogel
Aug 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Nanhai HeQiang Zhou
Sep 8, 2011·Proceedings of the National Academy of Sciences of the United States of America·Debabrata BiswasRobert G Roeder
Oct 30, 2009·The Journal of Biological Chemistry·Mary Rose ReisenauerWenzheng Zhang
Feb 18, 2010·The Journal of Biological Chemistry·Jeffrey J Lin, Charles S Hemenway
Jan 25, 2011·Briefings in Functional Genomics·Iris Uribesalgo, Luciano Di Croce
Sep 26, 2009·Nucleic Acids Research·Floor FrederiksFred van Leeuwen
Dec 10, 2009·Current Opinion in Nephrology and Hypertension·L Lee HammKathleen S Hering-Smith
Feb 24, 2009·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Julia M SchulzeMichael S Kobor
Jan 27, 2012·American Journal of Physiology. Cell Physiology·Yawar J QadriCatherine M Fuller
Apr 30, 2010·American Journal of Physiology. Renal Physiology·Mary Rose ReisenauerWenzheng Zhang
May 14, 2010·American Journal of Physiology. Renal Physiology·Louisa M Villeneuve, Rama Natarajan
Dec 16, 2011·American Journal of Physiology. Renal Physiology·Emily BorstingRobyn Cunard
Nov 16, 2012·American Journal of Physiology. Renal Physiology·Wenzheng ZhangBruce C Kone
Mar 3, 2007·The Journal of Clinical Investigation·Wenzheng ZhangBruce C Kone
Mar 3, 2007·The Journal of Clinical Investigation·David Pearce, Thomas R Kleyman
Dec 14, 2011·Hematology·Kathrin M Bernt, Scott A Armstrong
Dec 4, 2009·PLoS Biology·Dorothee MuellerRobert K Slany
Jan 18, 2013·PloS One·Hongyu WuWenzheng Zhang
Jan 12, 2013·Journal of the American Society of Nephrology : JASN·Hongyu WuWenzheng Zhang
May 3, 2014·Chromosoma·Antonia P M Jack, Sandra B Hake
Oct 6, 2014·Leukemia Research·Alyson A LokkenCharles S Hemenway
Sep 10, 2014·Journal of Endocrinological Investigation·Z-H TangK Zhang
Dec 29, 2013·Journal of Genetics·Zi-Hui TangLinuo Zhou
May 7, 2011·Journal of the American Society of Nephrology : JASN·Lihe ChenWenzheng Zhang
Sep 8, 2015·Epigenomics·Wenji YanMingzhou Guo
Sep 27, 2008·Kidney International·Dongyu ZhangBruce C Kone

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