Cis-regulatory determinants of MyoD function

Nucleic Acids Research
Vahab D SoleimaniMichael A Rudnicki

Abstract

Muscle-specific transcription factor MyoD orchestrates the myogenic gene expression program by binding to short DNA motifs called E-boxes within myogenic cis-regulatory elements (CREs). Genome-wide analyses of MyoD cistrome by chromatin immnunoprecipitation sequencing shows that MyoD-bound CREs contain multiple E-boxes of various sequences. However, how E-box numbers, sequences and their spatial arrangement within CREs collectively regulate the binding affinity and transcriptional activity of MyoD remain largely unknown. Here, by an integrative analysis of MyoD cistrome combined with genome-wide analysis of key regulatory histones and gene expression data we show that the affinity landscape of MyoD is driven by multiple E-boxes, and that the overall binding affinity-and associated nucleosome positioning and epigenetic features of the CREs-crucially depend on the variant sequences and positioning of the E-boxes within the CREs. By comparative genomic analysis of single nucleotide polymorphism (SNPs) across publicly available data from 17 strains of laboratory mice, we show that variant sequences within the MyoD-bound motifs, but not their genome-wide counterparts, are under selection. At last, we show that the quantitative regul...Continue Reading

References

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Citations

Nov 27, 2020·Frontiers in Physiology·Dathe Z Benissan-MessanPeter H U Lee
Nov 29, 2020·Current Opinion in Structural Biology·Ngaio C SmithJacqueline M Matthews
Apr 11, 2021·Nature Reviews. Molecular Cell Biology·Alexander Rauch, Susanne Mandrup

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Datasets Mentioned

BETA
GSE24811
GSE80588
GSM2131164
GSM2131165
GSM2131166
GSM2131167
GSM2131168
GSM2131169

Methods Mentioned

BETA
immnunoprecipitation
ChIP-seq
RNA-seq
Fluorescent Activated Cell Sorting
Tandem Affinity Purification
ChIP
the

Software Mentioned

MEMECHIP
Affymetrix
ENSEMBL
Illumina Cluster Station
MaSC
Pileup
Bioconductor R package
edgeR Bioconductor
MACS

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