PgmNr Z6109: Transcriptional Regulation of Heart Development in Zebrafish by ZNF143.

Authors:
L. E. Huning; Gary Kunkel


Institutes
Texas A&M University, College Station, TX.


Abstract:

Regulation of transcription in eukaryotes is an intricate interplay between activator/repressor proteins and co-regulator proteins that bind together to form a molecular machine. This regulation is tightly controlled to ensure that cells produce the correct amount of proteins needed for development. An important activator protein that binds over 2000 mammalian promoters is Zinc Finger Protein 143 (ZNF143). ZNF143 binds to promoter regions of both small RNA genes along with protein coding genes, and has been implicated in the regulation of promoters important for cell cycle progression. Knockdown experiments of this protein caused several pleiotropic effects during early embryogenesis in zebrafish including heart, blood, and brain phenotypes. Although ZNF143 is involved in many different cellular processes, the overall function and mechanism of molecular control at promoter regions of developmental genes is still largely unknown. Phenotypic analyses following knockdown of ZNF143 via antisense morpholinos reveal developmental defects in expression patterns of known heart marker genes at different stages during cardiogenesis. Preliminary ChIP-seq analysis with 24 hour embryos demonstrated that ZNF143 binds to over 500 promoter regions of genes, with 8% of these being bidirectional. Gene ontology analysis with these promoters showed that ZNF143 binds to genes involved in an assortment of biological processes including metabolism, cellular transport and organization, and developmental genes. Current studies involve a targeted CRISPR/Cas9 knockdown of ZNF143 and its effect on cardiogenesis. In addition, zebrafish transgenic lines are being constructed with several ZNF143 target promoters and binding-deficient versions to investigate the molecular mechanism of ZNF143. Hypothesized mechanistic activities of ZNF143 that will be assessed include the amount and timing of RNA polymerase II recruitment, different histone modifications, and nucleosomal patterns that occur at target ZNF143 bound promoter regions.



ZFIN Genetics Index
1. znf143b