Chromatin modules and their implication in genomic organization and gene regulation

Trends Genet. 2023 Feb;39(2):140-153. doi: 10.1016/j.tig.2022.11.003. Epub 2022 Dec 20.


Regulation of gene expression is a complex but highly guided process. While genomic technologies and computational approaches have allowed high-throughput mapping of cis-regulatory elements (CREs) and their interactions in 3D, their precise role in regulating gene expression remains obscure. Recent complementary observations revealed that interactions between CREs frequently result in the formation of small-scale functional modules within topologically associating domains. Such chromatin modules likely emerge from a complex interplay between regulatory machineries assembled at CREs, including site-specific binding of transcription factors. Here, we review the methods that allow identifying chromatin modules, summarize possible mechanisms that steer CRE interactions within these modules, and discuss outstanding challenges to uncover how chromatin modules fit in our current understanding of the functional 3D genome.

Keywords: chromatin modules; cis-regulatory elements; gene regulation; quantitative trait loci; topologically associating domains; transcription factors.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin* / genetics
  • Gene Expression Regulation* / genetics
  • Genome / genetics
  • Genomics
  • Regulatory Sequences, Nucleic Acid / genetics


  • Chromatin