Structural and functional analysis of the BMP-4 promoter in early embryos of Xenopus laevis.
The Xenopus laevis BMP-4 gene shows an evolutionary conserved structure containing two coding exons and a leader exon. The transcripts which are detected after zygotic activation of the gene in ventral mesoderm of late blastula stage embryos do either contain the leader exon or begin within the first intron. Luciferase reporter/promoter studies revealed multiple elements being required for the activation and for the spatial control of transcription. These elements are located within the upstream region and within the second intron and they interact with a most proximal located basal promoter being indispensable for transcriptional activation. The auto-activatory capacity of BMP-4 is mediated by several enhancer elements being responsive not only to BMP-4 but also to BMP-2 signaling. BMP-2 might thus function as a natural activator of the BMP-4 gene in the early embryo. Since reporter activity obtained with distinct BMP-2/4 responsive promoter deletion mutants is simultaneously inhibited by the dominant negative BMP receptor as well as by chordin, we suggest that down-regulation of the BMP-4 gene by chordin results from an interference with the auto-regulatory loop at the level of protein-protein interactions.
Metz
A
A
Abteilung Biochemie, Universität Ulm, Albert-Einstein-Allee 11, Germany.
Knöchel
S
S
Büchler
P
P
Köster
M
M
Knöchel
W
W
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D036703:Blastula / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D004742:Enhancer Elements, Genetic; D005091:Exons / Q000235:genetics; D025461:Feedback, Physiological; D005775:Gastrula / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D005796:Genes; D006023:Glycoproteins / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D007438:Introns; D008845:Microinjections; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics
D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; C054234:chordin