Pitx3 activates mouse tyrosine hydroxylase promoter via a high-affinity binding site

被引:70
作者
Lebel, M [1 ]
Gauthier, Y [1 ]
Moreau, A [1 ]
Drouin, J [1 ]
机构
[1] Clin Res Inst Montreal, Genet Mol Lab, Montreal, PQ H2W 1R7, Canada
关键词
homeodomain; MesDA neurons; Pitx3; TH; transcription;
D O I
10.1046/j.1471-4159.2001.00257.x
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
Tyrosine hydroxylase (TH) is the rate-limiting enzyme of dopamine and (nor)adrenaline biosynthesis. Regulation of its gene expression is complex and different regulatory mechanisms appear to be operative in various neuronal lineages. Pitx3, a homeodomain-containing transcription factor, has been cloned from neuronal tissues and, in the CNS, mouse Pitx3 is exclusively expressed in midbrain dopaminergic (MesDA) neurons from embryonic day 11 (Ell). TH appears in these neurons at E11.5, consistent with a putative role of Pitx3 in TH transcription. We show that Pitx3 activates the TH promoter through direct interaction with a single high-affinity binding site within the promoter and that this site is sufficient for Pitx3 responsiveness. In contrast, we did not observe an effect of Nurr1, an orphan nuclear receptor essential for normal development of MesDA neurons, on TH promoter activity. Pitx3 activation of TH promoter activity appears to be cell-dependent suggesting that Pitx3 action may be modulated by other(s) regulatory mechanism(s) and factor(s).
引用
收藏
页码:558 / 567
页数:10
相关论文
共 65 条
[1]   The molecular basis of Rieger syndrome - Analysis of Pitx2 homeodomain protein activities [J].
Amendt, BA ;
Sutherland, LB ;
Semina, EV ;
Russo, AF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (32) :20066-20072
[2]   DNA REGULATORY SEQUENCES OF THE RAT TYROSINE-HYDROXYLASE GENE DIRECT CORRECT CATECHOLAMINERGIC CELL-TYPE SPECIFICITY OF A HUMAN GROWTH-HORMONE REPORTER IN THE CNS OF TRANSGENIC MICE CAUSING A DWARF PHENOTYPE [J].
BANERJEE, SA ;
ROFFLERTARLOV, S ;
SZABO, M ;
FROHMAN, L ;
CHIKARAISHI, DM .
MOLECULAR BRAIN RESEARCH, 1994, 24 (1-4) :89-106
[3]   SEQUENCE AND EXPRESSION PATTERN OF THE STRA7 (GBX-2) HOMEOBOX-CONTAINING GENE INDUCED BY RETINOIC ACID IN P19 EMBRYONAL CARCINOMA-CELLS [J].
BOUILLET, P ;
CHAZAUD, C ;
OULADABDELGHANI, M ;
DOLLE, P ;
CHAMBON, P .
DEVELOPMENTAL DYNAMICS, 1995, 204 (04) :372-382
[4]   A response element for the homeodomain transcription factor Ptx3 in the tyrosine hydroxylase gene promoter [J].
Cazorla, P ;
Smidt, MP ;
O'Malley, KL ;
Burbach, JPH .
JOURNAL OF NEUROCHEMISTRY, 2000, 74 (05) :1829-1837
[5]   Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function [J].
Chiang, C ;
Ying, LTT ;
Lee, E ;
Young, KE ;
Corden, JL ;
Westphal, H ;
Beachy, PA .
NATURE, 1996, 383 (6599) :407-413
[6]   The PTX family of homeodomain transcription factors during pituitary developments [J].
Drouin, J ;
Lamolet, B ;
Lamonerie, T ;
Lanctôt, C ;
Tremblay, JJ .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1998, 140 (1-2) :31-36
[7]   SONIC-HEDGEHOG, A MEMBER OF A FAMILY OF PUTATIVE SIGNALING MOLECULES, IS IMPLICATED IN THE REGULATION OF CNS POLARITY [J].
ECHELARD, Y ;
EPSTEIN, DJ ;
STJACQUES, B ;
SHEN, L ;
MOHLER, J ;
MCMAHON, JA ;
MCMAHON, AP .
CELL, 1993, 75 (07) :1417-1430
[8]   Progression from extrinsic to intrinsic signaling in cell fate specification: A view from the nervous system [J].
Edlund, T ;
Jessell, TM .
CELL, 1999, 96 (02) :211-224
[9]   THE TRANSCRIPTION FACTOR, EGR-1, IS RAPIDLY MODULATED IN RESPONSE TO RETINOIC ACID IN P19 EMBRYONAL CARCINOMA-CELLS [J].
EDWARDS, SA ;
DARLAND, T ;
SOSNOWSKI, R ;
SAMUELS, M ;
ADAMSON, ED .
DEVELOPMENTAL BIOLOGY, 1991, 148 (01) :165-173
[10]  
Ericson J, 1997, COLD SPRING HARB SYM, V62, P451