The Evolution Of Transcription Factors Binding Sites Clustered Regions In Eukaryote

With the deepening of genomic research,the important role of non-coding regions of eukaryotic genomes in transcriptional regulation is constantly revealed.The non-coding regulatory regions of eukaryotes account for about 97% of the whole genome.There are many regulatory elements such as enhancers,promoters,and silencers.These regulatory elements not only have important biological functions,but also are closely related with many important diseases.In the non-coding regions of eukaryotes,a part of transcription factors(TF)binding regions and transcription factors constitute a complex transcriptional regulation system of eukaryotes,which has been a research hotspot in recent years.The regulatory mechanism of eukaryotic gene expression is very complicated.Multiple transcription factors bind in regulatory regions to control gene expression at different times and spaces.The complex and efficient evolutionary pressure lead to the different distribution of transcription factor binding sites(TFBSs)on the genome,which form a specific and unbalanced expression patterns.The research of epigenetics is constantly revealing the distribution of transcription factor binding regions.The prior research indicates that the transcription factors binding sites are highly cluster in C.elegans,Drosophila and human genome.In C.elegans,the number of transcription factors in clustered region has high correlation with nucleosome density,histone variation,and conserved replication inducing factors.In Drosophila,the complexity of transcription factors affects the gene expression level.In human,the number of different types of transcription factors is much higher than the expected model.Thus,it can be speculated that the transcription factors clustered regions facilitate the coordinated regulation of transcription factors and may have an evolutionary advantage.Basing on the algorithm developed by the DNaseI hypersensitive site and transcription factor motif,we identified the transcription factor binding sites clustered regions(TFCRs)in different species.TFCRs,as a region of the DNA segment capable of binding a large number of transcription factors,have important transcription regulatory functions and similar functions as enhancers.To provide a basis of studying the differences in transcription regulation of different species and help to further understand the regulatory functions of non-coding regions of the human genome,we analyzed TFCRs in transcriptional regulation mechanisms.In this study,we selected eight more distant species(6~1000 million years),including human,chimpanzee,rhesus,mouse,zebrafish,fly,worm and yeast,comparing the difference of TFCRs regulatory mechanism in different species.Our research focused on three aspects: First,by comparing the distribution of TFBSs on TFCRs between each species,we found that the distribution of TFBSs in different species was similar,but the number of TFBSs was different.Furthermore,by detailed analyzing the relationship between different classes of TFCRs and promoters,we found that the proportion of TFCRs falling into the promoter was constantly increasing with the TFCRs complexity in younger organisms(mouse,rhesus,chimpanzee and human),while the trend was not obvious in older organisms(yeast,worm,fly and zebrafish).Finally,by analyzing the effect of TFCRs in proximal regulation and remote regulation,we captured that the TFCRs regulatory mechanism in younger organisms was more complicated than older organisms.In zebrafish,mouse and human,there were steadily increasing gene expression with TFCRs complexity.It indicated that TFCRs complexity may have strong influence of gene expression.By comparing the differences of TFCRs regulation in different species,it was found that the transcriptional regulation pattern of TFCRs in younger organisms is more complicated than older organisms.