Heregulin-induced epigenetic regulation of the utrophin-A promoter.

Utpal Basu; Mads Gyrd-Hansen; Santhosh M Baby; Olga Lozynska; Thomas O B Krag; Claus J Jensen; Morten Frödin; Tejvir S Khurana

doi:10.1016/j.febslet.2007.07.021

Heregulin-induced epigenetic regulation of the utrophin-A promoter.

Utpal Basu, Mads Gyrd-Hansen, Santhosh M Baby, Olga Lozynska, Thomas O B Krag, Claus J Jensen, Morten Frödin, Tejvir S Khurana

13 Citations (Scopus)

Abstract

Utrophin is the autosomal homolog of dystrophin, the product of the Duchenne's muscular dystrophy (DMD) locus. Utrophin is of therapeutic interest since its over-expression can compensate dystrophin's absence. Utrophin is enriched at neuromuscular junctions due to heregulin-mediated utrophin-A promoter activation. We demonstrate that heregulin activated MSK1/2 and phosphorylated histone H3 at serine 10 in cultured C2C12 muscle cells, in an ERK-dependent manner. MSK1/2 inhibition suppressed heregulin-mediated utrophin-A activation. MSK1 over-expression potentiated heregulin-mediated utrophin-A activation and chromatin remodeling at the utrophin-A promoter. These results identify MSK1/2 as key effectors modulating utrophin-A expression as well as identify novel targets for DMD therapy.

Original language	English
Journal	FEBS Letters
Volume	581
Issue number	22
Pages (from-to)	4153-8
Number of pages	5
ISSN	0014-5793
DOIs	https://doi.org/10.1016/j.febslet.2007.07.021
Publication status	Published - 2007

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10.1016/j.febslet.2007.07.021

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@article{a3916070224e11ddbc23000ea68e967b,

title = "Heregulin-induced epigenetic regulation of the utrophin-A promoter.",

abstract = "Utrophin is the autosomal homolog of dystrophin, the product of the Duchenne's muscular dystrophy (DMD) locus. Utrophin is of therapeutic interest since its over-expression can compensate dystrophin's absence. Utrophin is enriched at neuromuscular junctions due to heregulin-mediated utrophin-A promoter activation. We demonstrate that heregulin activated MSK1/2 and phosphorylated histone H3 at serine 10 in cultured C2C12 muscle cells, in an ERK-dependent manner. MSK1/2 inhibition suppressed heregulin-mediated utrophin-A activation. MSK1 over-expression potentiated heregulin-mediated utrophin-A activation and chromatin remodeling at the utrophin-A promoter. These results identify MSK1/2 as key effectors modulating utrophin-A expression as well as identify novel targets for DMD therapy.",

author = "Utpal Basu and Mads Gyrd-Hansen and Baby, {Santhosh M} and Olga Lozynska and Krag, {Thomas O B} and Jensen, {Claus J} and Morten Fr{\"o}din and Khurana, {Tejvir S}",

note = "Keywords: Animals; Cells, Cultured; Chromatin Assembly and Disassembly; Enzyme Activation; Epigenesis, Genetic; Histones; Mice; Models, Genetic; Muscle Cells; Neuregulin-1; Phosphorylation; Promoter Regions (Genetics); Ribosomal Protein S6 Kinases, 90-kDa; Utrophin",

year = "2007",

doi = "10.1016/j.febslet.2007.07.021",

language = "English",

volume = "581",

pages = "4153--8",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "JohnWiley & Sons Ltd",

number = "22",

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TY - JOUR

T1 - Heregulin-induced epigenetic regulation of the utrophin-A promoter.

AU - Basu, Utpal

AU - Gyrd-Hansen, Mads

AU - Baby, Santhosh M

AU - Lozynska, Olga

AU - Krag, Thomas O B

AU - Jensen, Claus J

AU - Frödin, Morten

AU - Khurana, Tejvir S

N1 - Keywords: Animals; Cells, Cultured; Chromatin Assembly and Disassembly; Enzyme Activation; Epigenesis, Genetic; Histones; Mice; Models, Genetic; Muscle Cells; Neuregulin-1; Phosphorylation; Promoter Regions (Genetics); Ribosomal Protein S6 Kinases, 90-kDa; Utrophin

PY - 2007

Y1 - 2007

N2 - Utrophin is the autosomal homolog of dystrophin, the product of the Duchenne's muscular dystrophy (DMD) locus. Utrophin is of therapeutic interest since its over-expression can compensate dystrophin's absence. Utrophin is enriched at neuromuscular junctions due to heregulin-mediated utrophin-A promoter activation. We demonstrate that heregulin activated MSK1/2 and phosphorylated histone H3 at serine 10 in cultured C2C12 muscle cells, in an ERK-dependent manner. MSK1/2 inhibition suppressed heregulin-mediated utrophin-A activation. MSK1 over-expression potentiated heregulin-mediated utrophin-A activation and chromatin remodeling at the utrophin-A promoter. These results identify MSK1/2 as key effectors modulating utrophin-A expression as well as identify novel targets for DMD therapy.

AB - Utrophin is the autosomal homolog of dystrophin, the product of the Duchenne's muscular dystrophy (DMD) locus. Utrophin is of therapeutic interest since its over-expression can compensate dystrophin's absence. Utrophin is enriched at neuromuscular junctions due to heregulin-mediated utrophin-A promoter activation. We demonstrate that heregulin activated MSK1/2 and phosphorylated histone H3 at serine 10 in cultured C2C12 muscle cells, in an ERK-dependent manner. MSK1/2 inhibition suppressed heregulin-mediated utrophin-A activation. MSK1 over-expression potentiated heregulin-mediated utrophin-A activation and chromatin remodeling at the utrophin-A promoter. These results identify MSK1/2 as key effectors modulating utrophin-A expression as well as identify novel targets for DMD therapy.

U2 - 10.1016/j.febslet.2007.07.021

DO - 10.1016/j.febslet.2007.07.021

M3 - Journal article

C2 - 17692845

SN - 0014-5793

VL - 581

SP - 4153

EP - 4158

JO - FEBS Letters

JF - FEBS Letters

IS - 22

ER -

Heregulin-induced epigenetic regulation of the utrophin-A promoter.

Abstract

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