Time-dependent Pax3-mediated chromatin remodeling and cooperation with Six4 and Tead2 specify the skeletal myogenic lineage in developing mesoderm

PLoS Biology
Alessandro MagliRita C R Perlingeiro

Abstract

The transcriptional mechanisms driving lineage specification during development are still largely unknown, as the interplay of multiple transcription factors makes it difficult to dissect these molecular events. Using a cell-based differentiation platform to probe transcription function, we investigated the role of the key paraxial mesoderm and skeletal myogenic commitment factors-mesogenin 1 (Msgn1), T-box 6 (Tbx6), forkhead box C1 (Foxc1), paired box 3 (Pax3), Paraxis, mesenchyme homeobox 1 (Meox1), sine oculis-related homeobox 1 (Six1), and myogenic factor 5 (Myf5)-in paraxial mesoderm and skeletal myogenesis. From this study, we define a genetic hierarchy, with Pax3 emerging as the gatekeeper between the presomitic mesoderm and the myogenic lineage. By assaying chromatin accessibility, genomic binding and transcription profiling in mesodermal cells from mouse and human Pax3-induced embryonic stem cells and Pax3-null embryonic day (E)9.5 mouse embryos, we identified conserved Pax3 functions in the activation of the skeletal myogenic lineage through modulation of Hedgehog, Notch, and bone morphogenetic protein (BMP) signaling pathways. In addition, we demonstrate that Pax3 molecular function involves chromatin remodeling of i...Continue Reading

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Citations

May 28, 2019·Nature Communications·Alessandro MagliRita C R Perlingeiro
Jul 14, 2019·Journal of Muscle Research and Cell Motility·Fiona C Wardle
Apr 6, 2020·Seminars in Cell & Developmental Biology·Pascal MaireMaud Wurmser
Apr 20, 2021·Frontiers in Cell and Developmental Biology·Joana Esteves de LimaFrédéric Relaix
Oct 2, 2021·Cell Regeneration·Joana Esteves de Lima, Frédéric Relaix

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Datasets Mentioned

BETA
GSE125203

Methods Mentioned

BETA
fluorescence-activated cell sorting
ChIP-seq
immunoprecipitation
ChIP
RNA-seq
reverse transcription
transgenic
PCR
FACS
genotyping

Software Mentioned

Encode
Seqpos
IGV
R
R Bioconductor package
BEDTools map
GREAT
Illumina
Wig
Trimmomatic

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