An intron control region differentially regulates expression of thyroid hormone receptor β2 in the cochlea, pituitary, and cone photoreceptors

被引:48
作者
Jones, Iwan
Ng, Lily
Liu, Hong
Forrest, Douglas
机构
[1] NIDDKD, NIH, Clin Endocrinol Branch, Bethesda, MD 20892 USA
[2] CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA
关键词
D O I
10.1210/me.2007-0037
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The Thrb gene, encoding thyroid hormone receptor beta (TR beta), serves key roles in endocrine regulation and the development of the senses of hearing and color vision. The versatile functions of this gene depend upon its expression of distinct receptor isoforms by differential promoter activation. The TR beta 2 isoform has a particularly specialized distribution including in the anterior pituitary and cochlea. TR beta 2 is also found in immature cone photoreceptors where it has a unique role in programming the expression pattern of opsin photopigments that mediate color vision. Given the importance of precise, tissue-specific expression for the function of TR beta 2, we investigated the genomic control elements that direct this expression in vivo using lacZ reporter transgenes in mice. The TR beta 2 promoter region is sufficient for cochlear expression, whereas a complex intron control region is necessary for pituitary and retinal expression. In the retina, the intron region directs peak expression in the embryo in postmitotic, immature cones. The retinal control region is further subdivided into domains that specify and amplify expression, respectively, indicating that timely, cone-specific expression reflects an integrated response to complex signals. The mammalian Thrb gene has therefore incorporated several mechanisms into a multifunctional intron control region that regulates developmental induction of the distant promoter. This specialized genomic organization underlies the unique expression pattern and functions of TR beta 2.
引用
收藏
页码:1108 / 1119
页数:12
相关论文
共 56 条
[1]   Divergent roles for thyroid hormone receptor β isoforms in the endocrine axis and auditory system [J].
Abel, ED ;
Boers, ME ;
Pazos-Moura, C ;
Moura, E ;
Kaulbach, H ;
Zakaria, M ;
Lowell, B ;
Radovick, S ;
Liberman, MC ;
Wondisford, F .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (03) :291-300
[2]   Critical role for thyroid hormone receptor β2 in the regulation of paraventricular thyrotropin-releasing hormone neurons [J].
Abel, ED ;
Ahima, RS ;
Boers, ME ;
Elmquist, JK ;
Wondisford, FE .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (08) :1017-1023
[3]   Perspectives in the study of thyroid hormone action on brain development and function [J].
Bernal, J ;
Guadaño-Ferraz, A ;
Morte, B .
THYROID, 2003, 13 (11) :1005-1012
[4]   Normal timing of oligodendrocyte development depends on thyroid hormone receptor alpha 1 (TRα1) [J].
Billon, N ;
Jolicoeur, C ;
Tokumoto, Y ;
Vennström, B ;
Raff, M .
EMBO JOURNAL, 2002, 21 (23) :6452-6460
[5]  
BLANKS JC, 1984, INVEST OPHTH VIS SCI, V25, P546
[6]   ALPHA-THYROID AND BETA-THYROID HORMONE-RECEPTOR (TR) GENE-EXPRESSION DURING AUDITORY NEUROGENESIS - EVIDENCE FOR TR ISOFORM-SPECIFIC TRANSCRIPTIONAL REGULATION IN-VIVO [J].
BRADLEY, DJ ;
TOWLE, HC ;
YOUNG, WS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (02) :439-443
[7]  
BRADLEY DJ, 1992, J NEUROSCI, V12, P2288
[8]   RODS AND CONES IN THE MOUSE RETINA .2. AUTORADIOGRAPHIC ANALYSIS OF CELL GENERATION USING TRITIATED-THYMIDINE [J].
CARTERDAWSON, LD ;
LAVAIL, MM .
JOURNAL OF COMPARATIVE NEUROLOGY, 1979, 188 (02) :263-272
[9]   Cell fate determination in the vertebrate retina [J].
Cepko, CL ;
Austin, CP ;
Yang, XJ ;
Alexiades, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (02) :589-595
[10]  
CHATTERJEE VKK, 2001, ENDOCRINOLOGY, P1609