2. Academic Validation
  3. Footprint-C reveals transcription factor modes in local clusters and long-range chromatin interactions

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

  • Nat Commun. 2024 Dec 30;15(1):10922. doi: 10.1038/s41467-024-55403-7.
Xiaokun Liu # 1 2 3,  Hanhan Wei # 1 2 3,  Qifan Zhang 1 2 3,  Na Zhang 4,  Qingqing Wu 4,  Chenhuan Xu 5 6 7
Affiliations

Affiliations

  • 1 China National Center for Bioinformation, Beijing, China.
  • 2 Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
  • 3 University of Chinese Academy of Sciences, Beijing, China.
  • 4 Department of Ultrasound, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China.
  • 5 China National Center for Bioinformation, Beijing, China. xuchh@big.ac.cn.
  • 6 Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China. xuchh@big.ac.cn.
  • 7 University of Chinese Academy of Sciences, Beijing, China. xuchh@big.ac.cn.
  • # Contributed equally.
PMID: 39738122 DOI: 10.1038/s41467-024-55403-7
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.

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