PUBLICATION
Transcriptional regulatory elements of hif1α in distal locus of islet1 in Xenopus laevis
- Authors
- Miyakawa, M., Katada, T., Numa, Y., Kinoshita, T.
- ID
- ZDB-PUB-210401-2
- Date
- 2021
- Source
- Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 255: 110598 (Journal)
- Registered Authors
- Keywords
- Distal enhancer, Evolutional changes, Transcriptional regulation
- MeSH Terms
-
- Animals
- Genetic Loci*
- Hypoxia-Inducible Factor 1, alpha Subunit/genetics
- Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
- Mice
- Myocardium/metabolism*
- Response Elements*
- Transcription, Genetic*
- Xenopus Proteins/genetics
- Xenopus Proteins/metabolism*
- Xenopus laevis
- PubMed
- 33785414 Full text @ Comp. Biochem. Physiol. B Biochem. Mol. Biol.
Citation
Miyakawa, M., Katada, T., Numa, Y., Kinoshita, T. (2021) Transcriptional regulatory elements of hif1α in distal locus of islet1 in Xenopus laevis. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology. 255:110598.
Abstract
Adult mammalian hearts are not regenerative. However, recent studies have evidenced that hypoxia enhances their regeneration. Islet1 (isl1) is known as a cardiac progenitor marker, which is quiescent in adult mammal hearts. In Xenopus hearts, transcriptional activation of isl1 was shown during cardiac regeneration of froglets at 3 months after metamorphosis. In this study, we examined transcriptional regulation of isl1 focusing on hypoxia-inducible factor 1α (hif1α) in Xenopus heart. We found that hif1α expression was increased in response to cardiac injury and overexpression of hif1α upregulated mRNA expression of isl1. Multiple conservation analysis including 9 species revealed that 8 multiple conserved regions (MCRs) were present upstream of isl1. DNA sequence analysis using JASPAR showed hif1α binding motifs in MCRs. By luciferase reporter assay and chromatin immunoprecipitation analysis, we found that hif1α directly bound to hif1α motifs in the most distant MCR8 and showed a specific transcriptional activity on the MCR8. In the luciferase assay using constructs carrying MCR8 without a responsive motif of hif1α, the reporter activity was lost. Pharmacologically inhibition of hif1α affected isl1 transcription and downstream events including cardiac phenotypes, suggesting functional defects of islet1. Contrarily in murine hearts, transcription of isl1 was unresponsive even after cryoinjury to adult hearts while hif1α mRNA was induced. In comparative analysis of multiple alignment, hif1α elements present in MCR8 of Xenopus or zebrafish were found to be disrupted as species are evolutionarily distant from Xenopus and zebrafish. Our results suggested an altered switch of isl1 transcription between mammals and Xenopus laevis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping