Footprint-C reveals transcription factor modes in local clusters and long-range chromatin interactions

Xiaokun Liu, Hanhan Wei, Qifan Zhang, Na Zhang, Qingqing Wu and Chenhuan Xu ()
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Xiaokun Liu: China National Center for Bioinformation
Hanhan Wei: China National Center for Bioinformation
Qifan Zhang: China National Center for Bioinformation
Na Zhang: Capital Medical University, Beijing Maternal and Child Health Care Hospital
Qingqing Wu: Capital Medical University, Beijing Maternal and Child Health Care Hospital
Chenhuan Xu: China National Center for Bioinformation

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract The proximity ligation-based Hi-C and derivative methods are the mainstream tools to study genome-wide chromatin interactions. These methods often fragment the genome using enzymes functionally irrelevant to the interactions per se, restraining the efficiency in identifying structural features and the underlying regulatory elements. Here we present Footprint-C, which yields high-resolution chromatin contact maps built upon intact and genuine footprints protected by transcription factor (TF) binding. When analyzed at one-dimensional level, the billions of chromatin contacts from Footprint-C enable genome-wide analysis at single footprint resolution, and reveal preferential modes of local TF co-occupancy. At pairwise contact level, Footprint-C exhibits higher efficiency in identifying chromatin structural features when compared with other Hi-C methods, segregates chromatin interactions emanating from adjacent TF footprints, and uncovers multiway interactions involving different TFs. Altogether, Footprint-C results suggest that rich regulatory modes of TF may underlie both local residence and distal chromatin interactions, in terms of TF identity, valency, and conformational configuration.

Date: 2024
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DOI: 10.1038/s41467-024-55403-7

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