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Accessible chromatin structure permits factors Sp1 and Sp3 to regulate human TGFBI gene expression.

Authors
 Jong-Joo Lee  ;  Keunhee Park  ;  Myeong Heon Shin  ;  Wook-Jin Yang  ;  Min-Ji Song  ;  Joo-Hong Park  ;  Tai-Soon Yong  ;  Eung Kweon Kim  ;  Hyoung-Pyo Kim 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.409(2) : 222-228, 2011 
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN
 0006-291X 
Issue Date
2011
MeSH
Cell Line ; Cell Line, Tumor ; Chromatin/chemistry ; Chromatin/metabolism* ; Extracellular Matrix Proteins/genetics* ; GeneExpressionRegulation* ; GeneKnockdown Techniques ; Histones/metabolism ; Humans ; Promoter Regions, Genetic ; RNA Interference ; RNA, Messenger/antagonists & inhibitors ; RNA, Messenger/biosynthesis ; Sp1Transcription Factor/genetics ; Sp1Transcription Factor/metabolism* ; Sp3Transcription Factor/genetics ; Sp3Transcription Factor/metabolism* ; Transforming Growth Factor beta/genetics*
Keywords
TGFBI ; Sp1 ; Sp3 ; Chromatin ; Transcription
Abstract
Transforming growth factor beta 1-induced (TGFBI) protein is an extracellular matrix (ECM) protein that is associated with other ECM proteins and functions as a ligand for various types of integrins. In this study, we investigated how human TGFBI expression is regulated in lung and breast cancer cells. We observed that the TGFBI promoter in A549 and MBA-MD-231 cells, which constitutively express TGFBI, existed in an open chromatin conformation associated with transcriptionally permissive histone modifications. Moreover, we found that TGFBI expression required Sp1 transcription elements that can bind transcription factors Sp1 and Sp3 in vitro. Occupancy of the TGFBI promoter by Sp1 and Sp3 in vivo was only observed in TGFBI-expressing cells, indicating that open chromatin conformation might facilitate the binding of Sp1 and Sp3 to the TGFBI promoter region. TGFBI promoter activity was impaired when Sp1 elements were mutated, but was increased when Sp1 or Sp3 factors was overexpressed. Furthermore, Sp1 inhibition in vivo by mithramycin A, as well as knockdown of Sp1 and/or Sp3 expression by short interfering RNA, significantly reduced TGFBI mRNA and protein levels. Thus, our data demonstrated that the expression of TGFBI is well correlated with chromatin conformation at the TGFBI promoter, and that factors Sp1 and Sp3 are the primary determinants for the control of constitutive expression of TGFBI gene.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X11007340
DOI
10.1016/j.bbrc.2011.04.127
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Tropica Medicine (열대의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eung Kweon(김응권) ORCID logo https://orcid.org/0000-0002-1453-8042
Kim, Hyoung Pyo(김형표) ORCID logo https://orcid.org/0000-0003-1441-8822
Park, Keun Hee(박근희)
Park, Joo Hong(박주홍)
Song, Min Ji(송민지)
Shin, Myeong Heon(신명헌) ORCID logo https://orcid.org/0000-0001-8207-6110
Yong, Tai Soon(용태순) ORCID logo https://orcid.org/0000-0002-3445-0769
Lee, Jong Joo(이종주)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/94354
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