A fast Myh super enhancer dictates adult muscle fiber phenotype through competitive interactions with the fast Myh genes

The contractile properties of adult myofibers are shaped by their Myosin heavy chain (MYH) isoform content. We identify by snATAC-seq a 42kb super-enhancer (SE) at the locus regrouping the fast Myh (fMyh) genes. By 4C-seq we show that active fMyh promoters interact with the SE by DNA looping, leading to the activation of a single promoter per nucleus. A rainbow mouse transgenic model of the locus including the SE recapitulates the endogenous spatio-temporal expression of adult fMyh genes. In situ deletion of the SE by CRISPR/Cas9 editing demonstrates its major role in the control of associated fMyh genes, and deletion of two fMyh genes at the locus reveals an active competition of the promoters for the shared SE. Last, by disrupting the organization of fMyh, we uncover positional heterogeneity within limb skeletal muscles that may underlie selective muscle susceptibility to damage in certain myopathies.

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Myosin heavy chain composition of different skeletal muscles in Large White and Meishan pigs1

Journal of Animal Science ◽

10.2527/2004.8271931x ◽

2004 ◽

Vol 82 (7) ◽

pp. 1931-1941 ◽

Cited By ~ 93

Author(s):

L. Lefaucheur ◽

D. Milan ◽

P. Ecolan ◽

C. Le Callennec

Keyword(s):

Myosin Heavy Chain ◽

Heavy Chain ◽

Skeletal Muscles ◽

Large White ◽

Chain Composition ◽

Myosin Heavy Chain Composition

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The relationship between slow and fast myosin heavy chain content, calpastatin and meat tenderness in different ovine skeletal muscles

Meat Science ◽

10.1016/j.meatsci.2004.06.021 ◽

2005 ◽

Vol 69 (1) ◽

pp. 17-25 ◽

Cited By ~ 61

Author(s):

A.Q. Sazili ◽

T. Parr ◽

P.L. Sensky ◽

S.W. Jones ◽

R.G. Bardsley ◽

...

Keyword(s):

Myosin Heavy Chain ◽

Heavy Chain ◽

Skeletal Muscles ◽

Meat Tenderness ◽

Fast Myosin ◽

Fast Myosin Heavy Chain ◽

The Relationship

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Red and white muscle development in the trout (Oncorhynchus mykiss) as shown by in situ hybridisation of fast and slow myosin heavy chain transcripts

Journal of Experimental Biology ◽

10.1242/jeb.204.12.2097 ◽

2001 ◽

Vol 204 (12) ◽

pp. 2097-2101 ◽

Cited By ~ 3

Author(s):

Pierre-Yves Rescan ◽

Bertrand Collet ◽

Cecile Ralliere ◽

Chantal Cauty ◽

Jean-Marie Delalande ◽

...

Keyword(s):

Myosin Heavy Chain ◽

Heavy Chain ◽

In Situ Hybridisation ◽

Slow Muscle ◽

Fast Muscle ◽

Slow Myosin ◽

Slow Myosin Heavy Chain ◽

And Migration ◽

Slow Myhc

SUMMARY The axial muscle of most teleost species consists of a deep bulk of fast-contracting white fibres and a superficial strip of slow-contracting red fibres. To investigate the embryological development of fast and slow muscle in trout embryos, we carried out single and double in situ hybridisation with fast and slow myosin heavy chain (MyHC)-isoform-specific riboprobes. This showed that the slow-MyHC-positive cells originate in a region of the somite close to the notochord. As the somite matures in a rostrocaudal progression, the slow-MyHC-positive cells appear to migrate radially away from the notochord to the lateral surface of the myotome, where they form the superficial strip of slow muscle. Surprisingly, the expression pattern of the fast MyHC showed that the differentiation of fast muscle commences in the medial domain of the somite before the differentiation and migration of the slow muscle precursors. Later, as the differentiation of fast muscle progressively spreads from the inside to the outside of the myotome, slow-MyHC-expressing cells become visible medially. Our observations that the initial differentiation of fast muscle takes place in proximity to axial structures and occurs before the differentiation and migration of slow muscle progenitors are not in accord with the pattern of muscle formation in teleosts previously described in the zebrafish Danio rerio, which is often used as the model organism in fishes.

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