On TADs and LADs: Spatial Control Over Gene Expression

Trends Genet. 2016 Aug;32(8):485-495. doi: 10.1016/j.tig.2016.05.004. Epub 2016 Jun 13.

Abstract

The combinatorial action of transcription factors drives cell-type-specific gene expression patterns. However, transcription factor binding and gene regulation occur in the context of chromatin, which modulates DNA accessibility. High-resolution chromatin interaction maps have defined units of chromatin that are in spatial proximity, called topologically associated domains (TADs). TADs can be further classified based on expression activity, replication timing, or the histone marks or non-histone proteins associated with them. Independently, other chromatin domains have been defined by their likelihood to interact with non-DNA structures, such as the nuclear lamina. Lamina-associated domains (LADs) correlate with low gene expression and late replication timing. TADs and LADs have recently been evaluated with respect to cell-type-specific gene expression. The results shed light on the relevance of these forms of chromatin organization for transcriptional regulation, and address specifically how chromatin sequestration influences cell fate decisions during organismal development.

Keywords: enhancer–promoter interaction; heterochromatin; long-range chromatin structure; nuclear envelope; topologically associated domains.

Publication types

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

MeSH terms

  • Chromatin / genetics*
  • DNA / genetics*
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation / genetics*
  • Nuclear Lamina / genetics
  • Nuclear Lamina / metabolism
  • Transcription Factors / genetics*

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Transcription Factors
  • DNA