A principled strategy for mapping enhancers to genes

Sci Rep. 2019 Jul 30;9(1):11043. doi: 10.1038/s41598-019-47521-w.

Abstract

Mapping enhancers to genes is a fundamental goal of modern biology. We have developed an innovative strategy that maps enhancers to genes in a principled manner. We illustrate its power by applying it to Myrf. Despite being a master regulator of oligodendrocytes, oligodendrocyte enhancers governing Myrf expression remain elusive. Since chromatin conformation capture studies have shown that a gene and its enhancer tend to be found in the same topologically associating domain (TAD), we started with the delineation of the Myrf TAD. A genome-wide map of putative oligodendrocyte enhancers uncovered 6 putative oligodendrocyte enhancers in the Myrf TAD, narrowing down the search space for Myrf enhancers from the entire genome to 6 loci in a principled manner. Epigenome editing experiments revealed that two of them govern Myrf expression for oligodendrocyte development. Our new method is simple, principled, and powerful, providing a systematic way to find enhancers that regulate the expression of a gene of interest. Since it can be applied to most cell types, it would greatly facilitate our effort to unravel transcriptional regulatory networks of diverse cell types.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cells, Cultured
  • Chromatin Assembly and Disassembly
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation, Developmental
  • Genetic Loci*
  • Mice
  • Oligodendroglia / cytology
  • Oligodendroglia / metabolism
  • Sequence Analysis, DNA / methods*
  • Transcription Factors / genetics*

Substances

  • Transcription Factors
  • myelin gene regulatory factor, mouse