The developmental and evolutionary characteristics of transcription factor binding site clustered regions based on an explainable machine learning model.

Journal: Nucleic acids research
PMID: 38813828

Abstract

Gene expression is temporally and spatially regulated by the interaction of transcription factors (TFs) and cis-regulatory elements (CREs). The uneven distribution of TF binding sites across the genome poses challenges in understanding how this distribution evolves to regulate spatio-temporal gene expression and consequent heritable phenotypic variation. In this study, chromatin accessibility profiles and gene expression profiles were collected from several species including mammals (human, mouse, bovine), fish (zebrafish and medaka), and chicken. Transcription factor binding sites clustered regions (TFCRs) at different embryonic stages were characterized to investigate regulatory evolution. The study revealed dynamic changes in TFCR distribution during embryonic development and species evolution. The synchronization between TFCR complexity and gene expression was assessed across species using RegulatoryScore. Additionally, an explainable machine learning model highlighted the importance of the distance between TFCR and promoter in the coordinated regulation of TFCRs on gene expression. Our results revealed the developmental and evolutionary dynamics of TFCRs during embryonic development from fish, chicken to mammals. These data provide valuable resources for exploring the relationship between transcriptional regulation and phenotypic differences during embryonic development.

Authors

  • Zhangyi Ouyang
    Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
  • Feng Liu
    Department of Vascular and Endovascular Surgery, The First Medical Center of Chinese PLA General Hospital, 100853 Beijing, China.
  • Wanying Li
    Academy of Military Medical Sciences, Beijing 100850, China.
  • Junting Wang
    Beijing Institute of Radiation Medicine, Beijing 100850, China.
  • Bijia Chen
    Academy of Military Medical Sciences, Beijing 100850, China.
  • Yang Zheng
    Provincial Key Laboratory of Informational Service for Rural Area of Southwestern Hunan, Shaoyang University, Shaoyang, China.
  • Yaru Li
    College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation (Shanghai), Ministry of Agriculture, Shanghai 201306, China; Shanghai Engineering Research Center of Aquatic-Product Processing and Preservation, Shanghai 201306, China.
  • Huan Tao
    Department of Evidence-based Medicine and clinical epidemiology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, ChengDu, 610041, China.
  • Xiang Xu
    Beijing Center for Disease Prevention and Control, Beijing, China.
  • Cheng Li
    College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, China.
  • Yuwen Cong
    Academy of Military Medical Sciences, Beijing 100850, China.
  • Hao Li
    Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Xiaochen Bo
    Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
  • Hebing Chen
    Beijing Institute of Radiation Medicine, Beijing 100850, China.

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