RRC ID 72278
Author Hua P, Badat M, Hanssen LLP, Hentges LD, Crump N, Downes DJ, Jeziorska DM, Oudelaar AM, Schwessinger R, Taylor S, Milne TA, Hughes JR, Higgs DR, Davies JOJ.
Title Defining genome architecture at base-pair resolution.
Journal Nature
Abstract In higher eukaryotes, many genes are regulated by enhancers that are 104-106 base pairs (bp) away from the promoter. Enhancers contain transcription-factor-binding sites (which are typically around 7-22 bp), and physical contact between the promoters and enhancers is thought to be required to modulate gene expression. Although chromatin architecture has been mapped extensively at resolutions of 1 kilobase and above; it has not been possible to define physical contacts at the scale of the proteins that determine gene expression. Here we define these interactions in detail using a chromosome conformation capture method (Micro-Capture-C) that enables the physical contacts between different classes of regulatory elements to be determined at base-pair resolution. We find that highly punctate contacts occur between enhancers, promoters and CCCTC-binding factor (CTCF) sites and we show that transcription factors have an important role in the maintenance of the contacts between enhancers and promoters. Our data show that interactions between CTCF sites are increased when active promoters and enhancers are located within the intervening chromatin. This supports a model in which chromatin loop extrusion1 is dependent on cohesin loading at active promoters and enhancers, which explains the formation of tissue-specific chromatin domains without changes in CTCF binding.
Volume 595(7865)
Pages 125-129
Published 2021-7-1
DOI 10.1038/s41586-021-03639-4
PII 10.1038/s41586-021-03639-4
PMID 34108683
MeSH Animals Base Pairing / genetics* Binding Sites CCCTC-Binding Factor / metabolism Cell Cycle Proteins / metabolism Cells, Cultured Chromatin / chemistry Chromatin / genetics Chromatin / metabolism Chromosomal Proteins, Non-Histone / metabolism Enhancer Elements, Genetic / genetics Erythroid Cells / cytology Erythroid Cells / metabolism Gene Expression Regulation Genome / genetics* Mice Mice, Inbred C57BL Organ Specificity Promoter Regions, Genetic / genetics alpha-Globins / genetics
IF 42.779
Human and Animal Cells HUDEP-2(RCB4557)