Systematic evaluation of chromosome conformation capture assays

Betul Akgol Oksuz, Liyan Yang, Sameer Abraham, Sergey V Venev, Nils Krietenstein, Krishna Mohan Parsi, Hakan Ozadam, Marlies E Oomen, Ankita Nand, Hui Mao, Ryan M J Genga, Rene Maehr, Oliver J Rando, Leonid A Mirny, Johan H Gibcus, Job Dekker.
Nat Methods. 2021-09-03;18(9):1046-1055.
Abstract
Chromosome conformation capture (3C) assays are used to map chromatin interactions genome-wide. Chromatin interaction maps provide insights into the spatial organization of chromosomes and the mechanisms by which they fold. Hi-C and Micro-C are widely used 3C protocols that differ in key experimental parameters including cross-linking chemistry and chromatin fragmentation strategy. To understand how the choice of experimental protocol determines the ability to detect and quantify aspects of chromosome folding we have performed a systematic evaluation of 3C experimental parameters. We identified optimal protocol variants for either loop or compartment detection, optimizing fragment size and cross-linking chemistry. We used this knowledge to develop a greatly improved Hi-C protocol (Hi-C 3.0) that can detect both loops and compartments relatively effectively. In addition to providing benchmarked protocols, this work produced ultra-deep chromatin interaction maps using Micro-C, conventional Hi-C and Hi-C 3.0 for key cell lines used by the 4D Nucleome project.
Datasets
DSR537RIC, DSR444FBP, DSR807ISC, DSR155TYW, DSR422CEP, DSR327HLB, DSR091MER, DSR180QGS, DSR055LFO, DSR737KGH, DSR391QNO, DSR700PCF, DSR684ZGS, DSR918CIC, DSR047QKB, DSR479GVD, DSR872POY, DSR048TYT, DSR653MUU, DSR066YTQ, DSR754YHM, DSR149PDL, DSR490EZC, DSR767WND, DSR572IKT, DSR254PGW, DSR289YIM, DSR451EJU, DSR157LBO, DSR896FIE, DSR811XDN, DSR671AAD, DSR549RIC, DSR124JOP, DSR507LIX, DSR586PLM, DSR731TDZ, DSR316HBX, DSR540FLU, DSR456FWD, DSR090OCI, DSR564AJF, DSR533TGW, DSR397ZND, DSR106XXT, DSR169IMD, DSR012WQO, DSR483MTK, DSR312WNM, DSR841NPK, DSR045HCZ, DSR748OFL, DSR969OFL, DSR891WEA, DSR567IUM, DSR497DAF, DSR119YGF, DSR499WVQ, DSR072SNV, DSR000VQE, DSR951IQG, DSR495LNB, DSR324ANW, DSR457HRL, DSR884KPT, DSR313XKJ, DSR378EON, DSR882XCP, DSR407FUO, DSR851OCU, DSR919SOB, DSR558JJA, DSR075HLG, DSR231TYR, DSR961WJW, DSR834ANZ, DSR223YPR, DSR636IVC, DSR311UIT, DSR852XHU, DSR721YOW, DSR437FIX, DSR287QTC, DSR037DPN, DSR832OKT, DSR654AVA, DSR949CFE, DSR049XUF, DSR181EFP, DSR010WGH, DSR725VAR, DSR139UBN, DSR310VWE, DSR613OLV, DSR915YYD, DSR737EQA, DSR538ETS, DSR290BVC, DSR440NHM, DSR544NFB, DSR665NMH, DSR845GYW, DSR680GUA, DSR229MMI, DSR459WFJ, DSR586GXI, DSR527MQI, DSR513QXR, DSR025KNY, DSR976HAN, DSR575SAL, DSR151HTH, DSR247WWZ, DSR718IEG, DSR366YRD, DSR710ZMS, DSR358YIW, DSR242UWU, DSR272NBQ, DSR998VIS, DSR345JDI, DSR585LXT, DSR792YFU, DSR111BUL, DSR056YFO, DSR638LLT, DSR707LEZ, DSR531OKL, DSR105EMA

Related data

Data summary
Data are available at GEO under accession number GSE163666. Supplementary Table 1 lists datasets accessible through the 4DN data portal including 4DN accession numbers. Source data are provided with this paper.
Available data
website
Data summary
Scripts and notebooks used in this paper can be accessed at https://github.com/dekkerlab/matrix_paper