Identification Of Epigenetic Modification State Of Transcription Factor Binding Sites In Plant And Construction Of Database

Gene expression regulation is the basis for the normal and orderly progress of many biological processes.At the transcriptional level,transcription factors and epigenetic modifications are the main factors affecting gene expression.Transcription factors bind to specific DNA sequences of cis-acting element,thereby activating or inhibiting gene transcription.Epigenetic modification can affect the binding of transcription factors to cisacting elements by changing the local chromosome structure,thus controlling the expression of genes.Therefore,epigenetic modification patterns around the binding site of transcription factor can be used to determine their regulatory activities.With the rapid development and wide application of high-throughput sequencing technology,a large amount of transcription factor binding sites data and epigenetic modifications data have been accumulated.The binding sites data are collected in various forms in different transcription factor binding sites database.Studies have shown that the binding of transcription factors is regulated by epigenetic modifications.Although a large number of databases of transcription factor binding sites have been reported in plants,such as PlantTFDB database,these databases have different emphasis on the study of transcription factor binding sites,and there is no report about the epigenetic modification states of transcription factor binding sites and their related functions.The correlation analysis between transcription factors and epigenetic modifications has been reported previously.However,they are limited to the study of individual transcription factors or apparent modifications in several cell lines.Therefore,the construction of a database integrating transcription factor binding sites and their epigenetic modifications states is helpful to provide professional data support for relevant research fields.In this study,we first downloaded the transcription factor binding sites data of Arabidopsis thaliana,Oryza saliva and Zea mays from four databases:PlantTFDB.JASPAR.Cis-BP and PlantCistromeDB.And the transcription factors core motifs on the whole gene were identified by bioinformatics method.Next,epigenetic modifications data of three species on NCBI and other public data platforms were integrated.ChromHMM was used to identify the genome-wide chromatin states of the three species,and Arabidopsis thaliana,Oryza sativa and Zea mays genomes were divided into 27,13,and 10 chromatin states,respectively.Moreover,k-means algorithm was used to cluster transcription factor binding sites according to epigenetic modifications data.The function of the transcription factor binding sites can be predicted by the epigenetic modifications pattern near the site.It is speculated that those transcription factor binding sites exhibit enrichment of epigenetic modifications with transcriptional activation,such as H3K4me3,H3K9ac,etc.,can promote gene expression.And those transcription factor binding sites exhibit enrichment of epigenetic modifications with transcriptional inhibition,such as H3K2 7me3,DNA methylation,etc.,can inhibit gene expression.In order to better illustrate the relationship between epigenetic modifications and transcription factors,RNA-seq data that corresponding to the period of epigenetic modification were also integrated in this study.Finally,to facilitate retrieval and subsequent analysis,relevant results were added to plant transcription factor binding sites and epigenetic modification database(petfDB,http://bioinfo.njau.edu.cn/petfdb/index.php).The database integrates information on transcription factor binding sites,chromatin state map and the correlation analysis between binding sites and epigenetic modifications of Arabidopsis thaliana,Oryza sativa and Zea mays.In addition,JBrowser was used as a visualization tool to display transcription factors data,epigenetic modifications data and RNA-seq data.Users can enter the protein sequence or sequence you interest in for comparative analysis to view its possible binding sites and the epigenetic modifications patterns near the binding site.The database can also be used to speculate the function of transcription factor binding sites and whether there is co-localization among transcription factors.In this paper,through the integration of transcription factor binding sites and epigenetic modifications data,the relationship between transcription factors and epigenetic modifications can be more comprehensively described,which lays the foundation for further research on transcription factors.