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Hoxc8 represses BMP-induced expression of Smad6

Authors
 Myengmo Kang  ;  Jinwoong Bok  ;  Custer C. Deocaris  ;  Hyoung Woo Park  ;  Myoung Hee Kim 
Citation
 MOLECULES AND CELLS, Vol.29(1) : 29-33, 2010 
Journal Title
 MOLECULES AND CELLS 
ISSN
 1016-8478 
Issue Date
2010
MeSH
Animals ; Body Patterning ; Bone Morphogenetic Proteins/metabolism* ; Cell Line ; Cloning, Molecular ; Feedback, Physiological ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism* ; Mesenchymal Stromal Cells/metabolism* ; Mesenchymal Stromal Cells/pathology ; Mice ; Protein Binding ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Smad1 Protein/genetics ; Smad1 Protein/metabolism* ; Smad6 Protein/genetics ; Smad6 Protein/metabolism* ; Transcriptional Activation
Keywords
bone morphogenetic protein (BMP) ; Hoxc8 ; Smad1 ; Smad6
Abstract
Proper regulation of bone morphogenetic protein (BMP) signaling is critical for correct patterning and morphogenesis of various tissues and organs. A well known feedback mechanism is a BMP-mediated induction of Smad6, an inhibitor of BMP signaling. Hoxc8, one of the Hox family transcription factors, has also been shown to negatively regulate BMP-mediated gene expression. Here we add another level of Hoxc8 regulation on BMP signaling. Our results show that Hoxc8, when over-expressed in C3H10T1/2 or C2C12 cells, suppressed basal Smad6 promoter activity and its mRNA expression. Activation of Smad6 transcription either by BMP2 treatment or Smad1 over-expression was also abolished by Hoxc8. When chromatin was precipitated from mouse embryos with anti-Smad1 or anti-Hoxc8 antibody, Smad6 promoter sequence was enriched, suggesting that Hoxc8 proteins make complexes with Smad1 in the Smad6 promoter region. Yet, a lack of Hox binding motifs in the Smad6 promoter sequence suggests that instead of directly binding to the DNA, Hoxc8 may regulate Smad6 expression via an indirect mechanism. Our results suggest that the Smad6-mediated negative feedback mechanism on BMP signaling may be balanced by the repression of Smad6 expression by Hoxc8.
Full Text
http://link.springer.com/article/10.1007%2Fs10059-010-0007-1
DOI
10.1007/s10059-010-0007-1
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Kang, Myengmo(강명모)
Kim, Myoung Hee(김명희) ORCID logo https://orcid.org/0000-0001-5652-1452
Park, Hyoung Woo(박형우) ORCID logo https://orcid.org/0000-0002-5341-9249
Bok, Jin Woong(복진웅) ORCID logo https://orcid.org/0000-0003-1958-1872
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/100598
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