Biased visibility in Hi-C datasets marks dynamically regulated condensed and decondensed chromatin states genome-wide

BMC Genomics

Prashanth Kumar Guthikonda¹  Rakhee Nayak¹  Srinivas Kethavath¹  Sreenivasulu Kurukuti¹  Monika Dass²  Kuljeet Singh Sandhu²  Harpreet Singh²  Keerthivasan Raanin Chandradoss² 

[1] Department of Animal Biology, School of Life Sciences, University of Hyderabad (UoH), Central University;Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) – Mohali;

关键词: Hi-C;    3D genome;    Chromatin condensation;    Lamina associated domains;    CTCF;   

DOI  :  10.1186/s12864-020-6580-6

来源: DOAJ

【 摘 要 】

Abstract Background Proximity ligation based techniques, like Hi-C, involve restriction digestion followed by ligation of formaldehyde cross-linked chromatin. Distinct chromatin states can impact the restriction digestion, and hence the visibility in the contact maps, of engaged loci. Yet, the extent and the potential impact of digestion bias remain obscure and under-appreciated in the literature. Results Through analysis of 45 Hi-C datasets, lamina-associated domains (LADs), inactive X-chromosome in mammals, and polytene bands in fly, we first established that the DNA in condensed chromatin had lesser accessibility to restriction endonucleases used in Hi-C as compared to that in decondensed chromatin. The observed bias was independent of known systematic biases, was not appropriately corrected by existing computational methods, and needed an additional optimization step. We then repurposed this bias to identify novel condensed domains outside LADs, which were bordered by insulators and were dynamically associated with the polycomb mediated epigenetic and transcriptional states during development. Conclusions Our observations suggest that the corrected one-dimensional read counts of existing Hi-C datasets can be reliably repurposed to study the gene-regulatory dynamics associated with chromatin condensation and decondensation, and that the existing Hi-C datasets should be interpreted with cautions.

【 授权许可】

Unknown