Identification and characterization of the human SOX6 promoter

被引:10
作者
Ikeda, Toshiyuki
Saito, Taku
Ushita, Masahiro
Yano, Fumiko
Kan, Akinorl
Itaka, Keiji
Moro, Toru
Nakamura, Kozo
Kawaguchi, Hiroshi
Chung, Ung-il
机构
[1] Univ Tokyo, Fac Med, Ctr Dis Biol & Integrat Med, Tokyo 1138655, Japan
[2] Univ Tokyo, Fac Med, Sensory & Motor Syst Med, Tokyo 1138655, Japan
关键词
Sox6; Sox9; cartilage; promoter; CCAAT enhancer binding protein (C/EBP);
D O I
10.1016/j.bbrc.2007.03.133
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The present study attempted to identify and characterize the embryonic promoter of Sox6, a determinant regulator of chondrogenic differentiation. A common transcription start region for human and mouse Sox6 was initially identified, which contained a highly conserved sequence, A-box. Tandem repeats of A-box had a strong transcriptional activity both at the basal level and in response to Sox9. Cells carrying the 4xA-box-DsRed2 reporter fluoresced only upon chondrogenic differentiation. The 46-bp core enhancer region (CES6) was then identified in the 3' half of A-box, within which a C/EBP-binding motif was identified. Overexpressed C/EBP beta activated the Sox6 promoter, and mutant 4xCES6 constructs lacking the C/EBP motif lost their basal activity. CES6 and nuclear extracts formed a specific complex, which was supershifted by anti-C/EBP beta antibody, and in vitro translated C/EBP beta specifically bound to CES6. Thus, we successfully identified the Sox6 promoter and its core enhancer and characterized the interactions with regulatory transcription factors. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:383 / 390
页数:8
相关论文
共 24 条
[1]   A NUCLEAR FACTOR FOR IL-6 EXPRESSION (NF-IL6) IS A MEMBER OF A C/EBP FAMILY [J].
AKIRA, S ;
ISSHIKI, H ;
SUGITA, T ;
TANABE, O ;
KINOSHITA, S ;
NISHIO, Y ;
NAKAJIMA, T ;
HIRANO, T ;
KISHIMOTO, T .
EMBO JOURNAL, 1990, 9 (06) :1897-1906
[2]   The transcrintion factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6 [J].
Akiyama, H ;
Chaboissier, MC ;
Martin, JF ;
Schedl, A ;
de Crombrugghe, B .
GENES & DEVELOPMENT, 2002, 16 (21) :2813-2828
[3]   Essential role of Sox9 in the pathway that controls formation of cardiac valves and septa [J].
Akiyama, H ;
Chaboissier, MC ;
Behringer, RR ;
Rowitch, DH ;
Schedl, A ;
Epstein, JA ;
de Crombrugghe, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (17) :6502-6507
[4]   Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J].
Altschul, SF ;
Madden, TL ;
Schaffer, AA ;
Zhang, JH ;
Zhang, Z ;
Miller, W ;
Lipman, DJ .
NUCLEIC ACIDS RESEARCH, 1997, 25 (17) :3389-3402
[5]   Haploinsufficiency of Sox9 results in defective cartilage primordia and premature skeletal mineralization [J].
Bi, WM ;
Huang, WD ;
Whitworth, DJ ;
Deng, JM ;
Zhang, ZP ;
Behringer, RR ;
de Crombrugghe, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (12) :6698-6703
[6]   Sox9 is required for cartilage formation [J].
Bi, WM ;
Deng, JM ;
Zhang, ZP ;
Behringer, RR ;
de Crombrugghe, B .
NATURE GENETICS, 1999, 22 (01) :85-89
[7]   Chondrocyte-specific enhancer elements in the Col11a2 gene resemble the Col2a1 tissue-specific enhancer [J].
Bridgewater, LC ;
Lefebvre, V ;
de Crombrugghe, B .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (24) :14998-15006
[8]  
Buckwalter Joseph A, 2005, Instr Course Lect, V54, P465
[9]   Cloning, characterization and chromosome mapping of the human SOX6 gene [J].
Cohen-Barak, G ;
Hagiwara, N ;
Arlt, MF ;
Horton, JP ;
Brilliant, MH .
GENE, 2001, 265 (1-2) :157-164
[10]   Transcriptional mechanisms of chondrocyte differentiation [J].
de Crombrugghe, B ;
Lefebvre, V ;
Behringer, RR ;
Bi, WM ;
Murakami, S ;
Huang, WD .
MATRIX BIOLOGY, 2000, 19 (05) :389-394