MEMBERS OF THE HNF-3 FORKHEAD FAMILY OF TRANSCRIPTION FACTORS EXHIBIT DISTINCT CELLULAR EXPRESSION PATTERNS IN LUNG AND REGULATE THE SURFACTANT PROTEIN-B PROMOTER

被引:120
作者
CLEVIDENCE, DE
OVERDIER, DG
PETERSON, RS
PORCELLA, A
YE, HG
PAULSON, KE
COSTA, RH
机构
[1] UNIV ILLINOIS,COLL MED,DEPT BIOCHEM MC 536,CHICAGO,IL 60612
[2] TUFTS UNIV,USDA,HUMAN NUTR RES CTR AGING,BOSTON,MA 02111
关键词
D O I
10.1006/dbio.1994.1307
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The hepatocyte nuclear factor 3 (HNF-3)/fork head (fkh) proteins consist of an extensive family of tissue-specific and developmental gene regulators which share homology within the winged helix DNA binding motif. We report on the isolation of a new family member, HNF-3/forkhead homolog 8 (HFH-8), from lung cDNA libraries and the derivation of the complete amino acid sequences for the HFH-8 protein as well as previously identified HFH-1 and HFH-4 proteins. The HFH proteins contain several sequence motifs found in activation domains of other transcription factors and HNF-3/fkh family members. In situ hybridization with the HNF-3, HFH-4, and HFH-8 probes in adult lung demonstrate that the HNF-3/fkh cellular expression patterns are regionally specified. Whereas HNF-3 alpha and HNF-3 beta are normally coexpressed in the hepatocyte, their expression patterns in the lung are different. The HNF-3 alpha and HFH-4 genes are coexpressed in the bronchiolar epithelium (clara cells), whereas the HNF-3 beta probe exhibits prominent hybridization with the smooth muscle surrounding arterioles and bronchioles. In contrast, HFH-8 probes labeled the type II pneumocyte cells lining the respiratory surfaces of terminal bronchioles and alveolar sac. We have identified an HNF-3 consensus DNA binding sequence in the proximal surfactant protein B (SPB) promoter region (SPB-f2, -78 to -88). SPB gene transcription is restricted to bronchiolar and alveolar epithelium which colocalizes with the expression pattern of the HNF-3 alpha and HFH-8 genes, respectively. We show that the SPB-f2 sequence is recognized by both HNF-3 alpha and HFH-8 proteins and that these cDNA expression vectors activate the SPB promoter in cotransfection assays through the HNF-3 consensus sequence. Our results suggest that SPB promoter activity is regulated by HNF-3 alpha and HFH-8 proteins in a cell type-specific manner. (C) 1994 Academic Press, Inc.
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页码:195 / 209
页数:15
相关论文
共 54 条
[1]   GENOMIC ELEMENTS INVOLVED IN TRANSCRIPTIONAL REGULATION OF THE RABBIT SURFACTANT PROTEIN-A GENE [J].
ALCORN, JL ;
GAO, E ;
CHEN, Q ;
SMITH, ME ;
GERARD, RD ;
MENDELSON, CR .
MOLECULAR ENDOCRINOLOGY, 1993, 7 (08) :1072-1085
[2]   ECTOPIC NEURAL EXPRESSION OF A FLOOR PLATE MARKER IN FROG EMBRYOS INJECTED WITH THE MIDLINE TRANSCRIPTION FACTOR PINTALLAVIS [J].
ALTABA, ARI ;
COX, C ;
JESSELL, TM ;
KLAR, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (17) :8268-8272
[3]   SEQUENTIAL EXPRESSION OF HNF-3-BETA AND HNF-3-ALPHA BY EMBRYONIC ORGANIZING CENTERS - THE DORSAL LIP/NODE, NOTOCHORD AND FLOOR PLATE [J].
ALTABA, ARI ;
PREZIOSO, VR ;
DARNELL, JE ;
JESSELL, TM .
MECHANISMS OF DEVELOPMENT, 1993, 44 (2-3) :91-108
[4]  
ALTABA RI, 1991, DEVELOPMENT, V116, P81
[5]  
ANG SL, 1993, DEVELOPMENT, V119, P1301
[6]   IDENTIFICATION OF HEPATOCYTE NUCLEAR FACTOR-III BINDING-SITES IN THE CLARA CELL SECRETORY PROTEIN GENE [J].
BINGLE, CD ;
GITLIN, JD .
BIOCHEMICAL JOURNAL, 1993, 295 :227-232
[7]  
BOHINSKI RJ, 1993, J BIOL CHEM, V268, P11160
[8]   XFKH2, A XENOPUS HNF-3-ALPHA HOMOLOG, EXHIBITS BOTH ACTIVIN-INDUCIBLE AND AUTONOMOUS PHASES OF EXPRESSION IN EARLY EMBRYOS [J].
BOLCE, ME ;
HEMMATIBRIVANLOU, A ;
HARLAND, RM .
DEVELOPMENTAL BIOLOGY, 1993, 160 (02) :413-423
[9]   CO-CRYSTAL STRUCTURE OF THE HNF-3/FORK HEAD DNA-RECOGNITION MOTIF RESEMBLES HISTONE-H5 [J].
CLARK, KL ;
HALAY, ED ;
LAI, ES ;
BURLEY, SK .
NATURE, 1993, 364 (6436) :412-420
[10]   IDENTIFICATION OF 9 TISSUE-SPECIFIC TRANSCRIPTION FACTORS OF THE HEPATOCYTE NUCLEAR FACTOR-III FORKHEAD DNA-BINDING-DOMAIN FAMILY [J].
CLEVIDENCE, DE ;
OVERDIER, DG ;
TAO, WF ;
QIAN, XB ;
PANI, L ;
LAI, EE ;
COSTA, RH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (09) :3948-3952