Antisense targeting of CXXC finger protein 1 inhibits genomic cytosine methylation and primitive hematopoiesis in zebrafish.

摘要: CXXC finger protein 1 (CFP1) binds to unmethylated CpG dinucleotides and is a component of the Set1 histone methyltransferase complex. Mice lacking CFP1 suffer peri-implantation lethal phenotype, CFP1-deficient embryonic stem cells are viable but unable differentiate exhibit 60-80% decrease in genomic cytosine methylation. A zebrafish homolog has been identified, ∼70% similar murine CFP1, widely expressed during development. Zebrafish embryos treated with zCFP1 antisense morpholino oligonucleotide had little or no circulating red blood exhibited abnormal yolk sac morphology at 48 h post-fertilization. Many antisense-treated also cardiac edema, 14% were dead 24 Morphant elevated levels apoptosis, particularly intermediate cell mass, site primitive erythropoiesis, as well aberrations vascular Genomic DNA isolated from morphant 60% reduction global phenotype was observed an independent oligonucleotide, not following injection unrelated control oligonucleotide. The rescued when mRNA encoding co-injected data base analysis reveals presence second version (zCFP1b). However, specific depletion indicates that these related genes have nonredundant functions controlling normal hematopoiesis epigenetic regulation. These findings establish importance postgastrulation