Numerous studies of relationship between epigenomic features have focused on their strong correlation across the genome,likely because such relationship can be easily identified by many established methods for correla...Numerous studies of relationship between epigenomic features have focused on their strong correlation across the genome,likely because such relationship can be easily identified by many established methods for correlation analysis.However,two features with little correlation may still colocalize at many genomic sites to implement important functions.There is no bioinformatic tool for researchers to specifically identify such feature pairs.Here,we develop a method to identify feature pairs in which two features have maximal colocalization minimal correlation(MACMIC)across the genome.By MACMIC analysis of 3306 feature pairs in 16 human cell types,we reveal a dual role of CCCTC-binding factor(CTCF)in epigenetic regulation of cell identity genes.Although super-enhancers are associated with activation of target genes,only a subset of super-enhancers colocalized with CTCF regulate cell identity genes.At super-enhancers colocalized with CTCF,CTCF is required for the active marker H3 K27 ac in cell types requiring the activation,and also required for the repressive marker H3 K27 me3 in other cell types requiring repression.Our work demonstrates the biological utility of the MACMIC analysis and reveals a key role for CTCF in epigenetic regulation of cell identity.The code for MACMIC is available at https://github.com/bxia888/MACMIC.展开更多
基金supported in part by the grants from National Institutes of Health(NIH)(Grant Nos.R01GM125632 to KC,R01HL133254 and R01HL148338 to JPC and KC,R01CA207098 and R01CA207109 to ML)QC is supported by the U.S.Department of Defense(Grant Nos.W81XWH17-1-0357 and W81XWH-19-1-0563)+2 种基金the American Cancer Society(Grant No.RSG-15-192-01)the National Cancer Institute(NCI),NIH(Grant Nos.R01CA208257 and P50CA180995 DRP)the Northwestern University Polsky Urologic Cancer Institute,USA
文摘Numerous studies of relationship between epigenomic features have focused on their strong correlation across the genome,likely because such relationship can be easily identified by many established methods for correlation analysis.However,two features with little correlation may still colocalize at many genomic sites to implement important functions.There is no bioinformatic tool for researchers to specifically identify such feature pairs.Here,we develop a method to identify feature pairs in which two features have maximal colocalization minimal correlation(MACMIC)across the genome.By MACMIC analysis of 3306 feature pairs in 16 human cell types,we reveal a dual role of CCCTC-binding factor(CTCF)in epigenetic regulation of cell identity genes.Although super-enhancers are associated with activation of target genes,only a subset of super-enhancers colocalized with CTCF regulate cell identity genes.At super-enhancers colocalized with CTCF,CTCF is required for the active marker H3 K27 ac in cell types requiring the activation,and also required for the repressive marker H3 K27 me3 in other cell types requiring repression.Our work demonstrates the biological utility of the MACMIC analysis and reveals a key role for CTCF in epigenetic regulation of cell identity.The code for MACMIC is available at https://github.com/bxia888/MACMIC.
