PMID- 32864204 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2167-8359 (Print) IS - 2167-8359 (Electronic) IS - 2167-8359 (Linking) VI - 8 DP - 2020 TI - Cumulative contact frequency of a chromatin region is an intrinsic property linked to its function. PG - e9566 LID - 10.7717/peerj.9566 [doi] LID - e9566 AB - Regulation of gene transcription is a complex process controlled by many factors, including the conformation of chromatin in the nucleus. Insights into chromatin conformation on both local and global scales can be provided by the Hi-C (high-throughput chromosomes conformation capture) method. One of the drawbacks of Hi-C analysis and interpretation is the presence of systematic biases, such as different accessibility to enzymes, amplification, and mappability of DNA regions, which all result in different visibility of the regions. Iterative correction (IC) is one of the most popular techniques developed for the elimination of these systematic biases. IC is based on the assumption that all chromatin regions have an equal number of observed contacts in Hi-C. In other words, the IC procedure is equalizing the experimental visibility approximated by the cumulative contact frequency (CCF) for all genomic regions. However, the differences in experimental visibility might be explained by biological factors such as chromatin openness, which is characteristic of distinct chromatin states. Here we show that CCF is positively correlated with active transcription. It is associated with compartment organization, since compartment A demonstrates higher CCF and gene expression levels than compartment B. Notably, this observation holds for a wide range of species, including human, mouse, and Drosophila. Moreover, we track the CCF state for syntenic blocks between human and mouse and conclude that active state assessed by CCF is an intrinsic property of the DNA region, which is independent of local genomic and epigenomic context. Our findings establish a missing link between Hi-C normalization procedures removing CCF from the data and poorly investigated and possibly relevant biological factors contributing to CCF. CI - (c)2020 Samborskaia et al. FAU - Samborskaia, Margarita D AU - Samborskaia MD AD - Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia. FAU - Galitsyna, Aleksandra AU - Galitsyna A AD - Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia. AD - A.A. Kharkevich Institute for Information Transmission Problems, RAS, Moscow, Russia. AD - Institute of Gene Biology, RAS, Moscow, Russia. FAU - Pletenev, Ilya AU - Pletenev I AD - Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia. FAU - Trofimova, Anna AU - Trofimova A AD - Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia. FAU - Mironov, Andrey A AU - Mironov AA AD - Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia. AD - A.A. Kharkevich Institute for Information Transmission Problems, RAS, Moscow, Russia. FAU - Gelfand, Mikhail S AU - Gelfand MS AD - Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia. AD - A.A. Kharkevich Institute for Information Transmission Problems, RAS, Moscow, Russia. FAU - Khrameeva, Ekaterina E AU - Khrameeva EE AD - Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia. LA - eng PT - Journal Article DEP - 20200810 PL - United States TA - PeerJ JT - PeerJ JID - 101603425 PMC - PMC7425636 OTO - NOTNLM OT - Chromatin OT - Compartments OT - Conformation capture OT - Hi-C COIS- Mikhail S. Gelfand is an Academic Editor for PeerJ. EDAT- 2020/08/31 06:00 MHDA- 2020/08/31 06:01 PMCR- 2020/08/10 CRDT- 2020/09/01 06:00 PHST- 2020/01/27 00:00 [received] PHST- 2020/06/27 00:00 [accepted] PHST- 2020/09/01 06:00 [entrez] PHST- 2020/08/31 06:00 [pubmed] PHST- 2020/08/31 06:01 [medline] PHST- 2020/08/10 00:00 [pmc-release] AID - 9566 [pii] AID - 10.7717/peerj.9566 [doi] PST - epublish SO - PeerJ. 2020 Aug 10;8:e9566. doi: 10.7717/peerj.9566. eCollection 2020.