The Study Of Cis-element And Trans-factor On A Novel Zinc Finger Protein ZNF333

Transcription regulation is crucial in controlling the gene expression in response to metabolic requirements, developmental programs and cell differentiation. Transcription factors are the key components in the transcription machinery of specific genes, while many transcription cofactors combine together with the transcription factors to orchestrate the whole transcription event. Nowadays, more and more transcription cofactors have been cloned and characterized in the field of human functional genomic study.Our research work mainly focuses on the functional study of zinc finger proteins. To a large extent, zinc finger protein families play an important role in eukaryotic gene regulation. In mammals, zinc finger proteins emerged as the largest and most prevalent families and their versatility maybe the result of dramatic evolutionary expansion. The zinc finger motif was firstly discovered as tandem element in the sequence of the TFIIIA protein. In addition to a zinc finger region, most of these proteins also contain a regulatory domain in the N terminal, which can be classified into different subfamilies. About 1/3 of ZFPs share a highly conserved KRAB domain which possibly have the function of transcriptional repression.A new KRAB zinc finger protein gene ZNF333, was identified in the critical region of a new polysyndactyly pedigree locus. High homologous KRAB domains have been predicted on the N terminal and a typical poly-zinc finger domain in C terminal by bioinformatics analysis. There are two alternative isoforms in ZNF333, one of transcripts has two KRAB domains and a 10 sets of C₂H₂ zinc finger structure, the other has only one KRAB domain without zinc finger domain by using a different transcription initiation site. As a sole gene containing duplicated KRAB domains currently, ZNF 333 has also several phosphorylation sites.In order to illustrate the function of ZNF333, it is important to obtain the clues of downstream target genes that it may regulate. To this aim, by using a random...