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zmiz1a zebrafish mutants have defective erythropoiesis, altered expression of autophagy genes, and a deficient response to vitamin D
- Source :
- Life sciences. 284
- Publication Year :
- 2021
-
Abstract
- ZMIZ1 is a transcriptional coactivator that is related to members of the protein inhibitor of activated STAT (PIAS) family. ZMIZ1 regulates the activity of various transcription factors including the androgen receptor, p53, and Smad3. ZMIZ1 also interacts with Notch1 and selectively regulates Notch1 target genes relevant for T cell development and leukemogenesis in mammals. Human ZMIZ1 is additionally characterized as a latitude-dependent autoimmune disease (LDAD) risk gene, as it is responsive to vitamin D and has been associated with at least eleven blood cell traits. To address the function of ZMIZ1 in fish, we introduced CRISPR/Cas9 mutations in the zmiz1a gene in zebrafish. We observed that inactivation of zmiz1a in developing zebrafish larvae results in lethality at 15 days post fertilization (dpf) and delayed erythroid maturation. Differential gene expression analysis indicated that 15 dpf zmiz1a-null larvae had altered expression of autophagy genes, and erythrocytes that lacked Zmiz1a function exhibited an accumulation of mitochondrial DNA. Furthermore, we observed that autophagy gene expression was dysregulated at earlier stages of development, which suggests the involvement of Zmiz1a in the regulation of autophagy genes beyond the process of red blood cell differentiation. Finally, we showed that the loss of Zmiz1a decreased the capacity of the embryos to respond to vitamin D, indicating additional participation of Zmiz1a as a mediator of vitamin D activity.
- Subjects :
- Embryo, Nonmammalian
Erythrocytes
Gene Dosage
Down-Regulation
Biology
General Biochemistry, Genetics and Molecular Biology
Hemoglobins
Mediator
Gene expression
Autophagy
Animals
Protein inhibitor of activated STAT
Erythropoiesis
General Pharmacology, Toxicology and Pharmaceutics
Vitamin D
Zebrafish
Gene
Transcription factor
Inflammation
Base Sequence
Cell Differentiation
General Medicine
Zebrafish Proteins
biology.organism_classification
Cell biology
Gene Expression Regulation
Mutation
Transcriptome
Subjects
Details
- ISSN :
- 18790631
- Volume :
- 284
- Database :
- OpenAIRE
- Journal :
- Life sciences
- Accession number :
- edsair.doi.dedup.....a817a17250ece62bf9e0af731b80c6e1