Regulation of collagen type I in vascular smooth muscle cells by competition between Nkx2.5 and deltaEF1/ZEB1

Molecular and Cellular Biology
Markella PonticosGeorge Bou-Gharios

Abstract

A major component of the vessel wall of large arteries and veins is the extracellular matrix (ECM), which consists of collagens, elastin, and proteoglycans. Collagen type I is one of the most abundant of the ECM proteins. We have previously shown that the pro-collagen type I alpha 2 gene contains an enhancer which confers tissue-specific expression in the majority of collagen-producing cells, including blood vessels. In this paper, we delineate a specific vascular smooth muscle cell (vSMC) element: a 100-bp sequence around -16.6 kb upstream of the transcription start site that regulates collagen expression exclusively in vSMCs. Furthermore, we show that the expression is activated through the binding of the homeodomain protein Nkx2.5, which is further potentiated in the presence of GATA6. In contrast, this element was repressed by the binding of the zinc-finger protein deltaEF1/ZEB1. We propose a model of regulation where the activating transcription factor Nkx2.5 and the repressor deltaEF1/ZEB1 compete for an overlapping DNA binding site. This element is important in understanding the molecular mechanisms of vessel remodeling and is a potential target for intervention in vascular diseases where there is excessive deposition of...Continue Reading

References

Aug 11, 1989·Nucleic Acids Research·D A BrennerL Veloz
Feb 1, 1994·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Z BogdanovicA C Lichtler
May 1, 1994·The Journal of Cell Biology·D J LiskaP Bornstein
Dec 1, 1995·Matrix Biology : Journal of the International Society for Matrix Biology·K NiederreitherB De Crombrugghe
Sep 15, 1996·Developmental Biology·R P Harvey
Apr 1, 1997·Molecular and Cellular Biology·V LefebvreB de Crombrugghe
Oct 6, 1997·The EMBO Journal·D DurocherM Nemer
Apr 17, 1998·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·R SekidoH Kondoh
Jan 14, 1999·The New England Journal of Medicine·R Ross
Jun 9, 1999·Proceedings of the National Academy of Sciences of the United States of America·A A Postigo, D C Dean
Jul 23, 1999·Mechanisms of Development·M TanakaS Izumo
May 16, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·R VirmaniS M Schwartz
Apr 20, 2001·Annals of Medicine·J Myllyharju, K I Kivirikko
Jan 5, 2002·The Journal of Biological Chemistry·Sarah De ValGeorge Bou-Gharios
Mar 6, 2002·Circulation·Peter LibbyAttilio Maseri
Aug 24, 2002·Endocrinology·Karen Sooy, Marie B Demay
Dec 17, 2002·Atherosclerosis·Gabriele A M PlenzWolfgang Völker
Dec 17, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Randolph L GearyLawrence D Adams
Jan 18, 2003·Developmental Cell·David F ChangRobert J Schwartz
Mar 5, 2003·The Journal of Biological Chemistry·Yuichiro J SuzukiBarry L Fanburg

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Citations

Nov 24, 2006·Journal of Materials Science. Materials in Medicine·G Jell, M M Stevens
Sep 9, 2005·The Journal of Experimental Medicine·Sergey FilippovStephen J Weiss
Jan 17, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Marpadga A ReddyRama Natarajan
Apr 28, 2009·American Journal of Respiratory Cell and Molecular Biology·Biao HuSem H Phan
Dec 31, 2009·PloS One·Jessica N SaykallyMichel M Sanders
Oct 31, 2012·PloS One·Abhishek SohniCatherine M Verfaillie
Jul 8, 2009·Clinical Journal of the American Society of Nephrology : CJASN·Mitsuo KatoRama Natarajan
Jun 16, 2012·Cardiology Research and Practice·Brigitte Laforest, Mona Nemer
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Mitsuo KatoRama Natarajan
Jul 8, 2014·Pharmaceutical Patent Analyst
Jun 9, 2016·Endocrine-related Cancer·Ahmad M AlamriPriscilla A Furth
Dec 8, 2016·Tissue Engineering. Part C, Methods·Minu Karthika GanesanPeter Petzelbauer
Apr 16, 2008·Experimental Hematology·Bryan McIntosh, Kenneth Kaushansky
Jan 18, 2018·Arthritis & Rheumatology·Athina DritsoulaMarkella Ponticos
Jun 15, 2018·Science Translational Medicine·Andriy O SamokhinBradley A Maron
Oct 30, 2004·Journal of Leukocyte Biology·Katherine A GaussMark T Quinn
Jan 21, 2018·Cell Death & Disease·Xiang ZhangShuang Yang
Oct 16, 2007·American Journal of Medical Genetics. Part a·Anthony J AldaveJulia E Richards
May 20, 2019·Cell Stress & Chaperones·Xiaoyan LiangYanyan Zhao
May 28, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Malina J IveyMichelle D Tallquist
Feb 23, 2019·International Journal of Molecular Sciences·Francisco SantosBruno Bernardes de Jesus
Jul 24, 2015·The Journal of Biological Chemistry·Houda BenlhabibCarole R Mendelson
Mar 3, 2020·Frontiers in Molecular Biosciences·Erik HenkeSüleyman Ergün
Oct 9, 2012·Biotechnology and Bioengineering·Julia J MackBrian N Cox
Feb 6, 2020·Journal of Translational Medicine·Hua-Tao WuJing Liu
Oct 28, 2016·Circulation Journal : Official Journal of the Japanese Circulation Society·Malina J Ivey, Michelle D Tallquist
Oct 20, 2020·Frontiers in Neurology·Byeong Jin HaMyung-Hoon Han
Apr 6, 2006·Cancer Research·Nicole S SpoelstraJennifer K Richer

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