A principled strategy for mapping enhancers to genes

Scientific Reports
Dongkyeong KimYungki Park

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.

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Citations

Sep 12, 2019·Human Molecular Genetics·Dongkyeong Kim, Yungki Park

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Datasets Mentioned

BETA
GSM1040155
GSM1040161
GSM1040164
GSM1040158
GSM1577134
GSM1587568

Methods Mentioned

BETA
transgenic
Hi-C
immunoprecipitation
ChIP-seq
RNA-seq
PCR
transfection

Software Mentioned

WASHU
liftOver
Epigenome Browswer
MACS2
CellProfiler
Myrf
Bowtie
GREAT

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