Preliminary Study On The Functions And Molecular Mechanisms Of YY2 In Gene Transcriptional Regulation

YY2(Yin Yang 2)is the paralog of YY1(Yin Yang 1),both of which belong to the transcription factor superfamily with zinc-finger domains.56%amino acid sequences in YY2 and YY1 are homologous,expecially in the zinc-finger regions,which can activate or repress gene transcription by directly binding to DNA[1]It is well known that YY1 plays a prevalent role in various types of cancers.However,the function of YY2 in tumorgenesis remains uncharacterized.In this thesis,we analyzed transcriptional events regulated by YY2 and binding sites of YY2 on chromatin by using global run-on coupled with high throughput sequencing(Gro-seq)and chromatin immunoprecipitation coupled with high throughput sequencing(ChIP-seq),respectively.The potential biological functions of YY2 were uncovered.To facilitate studying the biological functions of YY2 in vivo,we genereated yy2 knockout mice by using CRISPR/Cas9 gene editing technology.Specifically,we found that YY2 plays a dominant role in gene transcriptional activation,and focused on investigating the potential functions of the YY2-activated genes by doing gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.The most enriched GO terms for genes positively-regulated by YY2 included cell adhesion,sister chromatid cohesion,cell division and many other associated with the development of cancer.Subsequently,the genome-wide binding sites on chromatin of YY2 were systematically analyzed by using ChIP-seq.We found that 50%of YY2 binding sites were localized on promoter regions.Motif analysis revealed that the most enriched motif was the consensus sequence for YY1 DNA binding,which is consistent with previous report[1].Integration of the GRO-seq and ChIP-seq showed that YY2 binding at the promoter regions was highly correlated with gene transcriptional activation.Taken together,we integrated GRO-seq and ChIP-seq genome-wide data to systematically uncover the transcriptional events regulated by YY2 and the genomic regions bound by YY2,respectively.Furthermore,we generated yy2 knockout mice,which can provide an useful genetic model for further understanding the function of yy2 in vivo.