Chromatin regulated interchange between polycomb repressive complex 2 (PRC2)-Ezh2 and PRC2-Ezh1 complexes controls myogenin activation in skeletal muscle cells

Lovorka Stojic; Zusana Jasencakova; Carolina Prezioso; Alexandra Stützer; Beatrice Bodega; Diego Pasini; Rebecca Klingberg; Chiara Mozzetta; Raphael Margueron; Pier Lorenzo Puri; Dirk Schwarzer; Kristian Helin; Wolfgang Fischle; Valerio Orlando

doi:10.1186/1756-8935-4-16

Chromatin regulated interchange between polycomb repressive complex 2 (PRC2)-Ezh2 and PRC2-Ezh1 complexes controls myogenin activation in skeletal muscle cells

Lovorka Stojic, Zusana Jasencakova, Carolina Prezioso, Alexandra Stützer, Beatrice Bodega, Diego Pasini, Rebecca Klingberg, Chiara Mozzetta, Raphael Margueron, Pier Lorenzo Puri, Dirk Schwarzer, Kristian Helin, Wolfgang Fischle, Valerio Orlando

83 Citations (Scopus)

Abstract

Background: Polycomb group (PcG) genes code for chromatin multiprotein complexes that are responsible for maintaining gene silencing of transcriptional programs during differentiation and in adult tissues. Despite the large amount of information on PcG function during development and cell identity homeostasis, little is known regarding the dynamics of PcG complexes and their role during terminal differentiation. Results: We show that two distinct polycomb repressive complex (PRC)2 complexes contribute to skeletal muscle cell differentiation: the PRC2-Ezh2 complex, which is bound to the myogenin (MyoG) promoter and muscle creatine kinase (mCK) enhancer in proliferating myoblasts, and the PRC2-Ezh1 complex, which replaces PRC2-Ezh2 on MyoG promoter in post-mitotic myotubes. Interestingly, the opposing dynamics of PRC2-Ezh2 and PRC2-Ezh1 at these muscle regulatory regions is differentially regulated at the chromatin level by Msk1 dependent methyl/phospho switch mechanism involving phosphorylation of serine 28 of the H3 histone (H3S28ph). While Msk1/H3S28ph is critical for the displacement of the PRC2-Ezh2 complex, this pathway does not influence the binding of PRC2-Ezh1 on the chromatin. Importantly, depletion of Ezh1 impairs muscle differentiation and the chromatin recruitment of MyoD to the MyoG promoter in differentiating myotubes. We propose that PRC2-Ezh1 is necessary for controlling the proper timing of MyoG transcriptional activation and thus, in contrast to PRC2-Ezh2, is required for myogenic differentiation. Conclusions: Our data reveal another important layer of epigenetic control orchestrating skeletal muscle cell terminal differentiation, and introduce a novel function of the PRC2-Ezh1 complex in promoter setting.

Original language	English
Journal	Epigenetics & Chromatin
Volume	4
Number of pages	16
ISSN	1756-8935
DOIs	https://doi.org/10.1186/1756-8935-4-16
Publication status	Published - 5 Sept 2011

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Stojic, L., Jasencakova, Z., Prezioso, C., Stützer, A., Bodega, B., Pasini, D., Klingberg, R., Mozzetta, C., Margueron, R., Puri, P. L., Schwarzer, D., Helin, K., Fischle, W., & Orlando, V. (2011). Chromatin regulated interchange between polycomb repressive complex 2 (PRC2)-Ezh2 and PRC2-Ezh1 complexes controls myogenin activation in skeletal muscle cells. Epigenetics & Chromatin, 4. https://doi.org/10.1186/1756-8935-4-16

Stojic, L, Jasencakova, Z, Prezioso, C, Stützer, A, Bodega, B, Pasini, D, Klingberg, R, Mozzetta, C, Margueron, R, Puri, PL, Schwarzer, D, Helin, K, Fischle, W & Orlando, V 2011, 'Chromatin regulated interchange between polycomb repressive complex 2 (PRC2)-Ezh2 and PRC2-Ezh1 complexes controls myogenin activation in skeletal muscle cells', Epigenetics & Chromatin, vol. 4. https://doi.org/10.1186/1756-8935-4-16

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title = "Chromatin regulated interchange between polycomb repressive complex 2 (PRC2)-Ezh2 and PRC2-Ezh1 complexes controls myogenin activation in skeletal muscle cells",

abstract = "Background: Polycomb group (PcG) genes code for chromatin multiprotein complexes that are responsible for maintaining gene silencing of transcriptional programs during differentiation and in adult tissues. Despite the large amount of information on PcG function during development and cell identity homeostasis, little is known regarding the dynamics of PcG complexes and their role during terminal differentiation. Results: We show that two distinct polycomb repressive complex (PRC)2 complexes contribute to skeletal muscle cell differentiation: the PRC2-Ezh2 complex, which is bound to the myogenin (MyoG) promoter and muscle creatine kinase (mCK) enhancer in proliferating myoblasts, and the PRC2-Ezh1 complex, which replaces PRC2-Ezh2 on MyoG promoter in post-mitotic myotubes. Interestingly, the opposing dynamics of PRC2-Ezh2 and PRC2-Ezh1 at these muscle regulatory regions is differentially regulated at the chromatin level by Msk1 dependent methyl/phospho switch mechanism involving phosphorylation of serine 28 of the H3 histone (H3S28ph). While Msk1/H3S28ph is critical for the displacement of the PRC2-Ezh2 complex, this pathway does not influence the binding of PRC2-Ezh1 on the chromatin. Importantly, depletion of Ezh1 impairs muscle differentiation and the chromatin recruitment of MyoD to the MyoG promoter in differentiating myotubes. We propose that PRC2-Ezh1 is necessary for controlling the proper timing of MyoG transcriptional activation and thus, in contrast to PRC2-Ezh2, is required for myogenic differentiation. Conclusions: Our data reveal another important layer of epigenetic control orchestrating skeletal muscle cell terminal differentiation, and introduce a novel function of the PRC2-Ezh1 complex in promoter setting.",

author = "Lovorka Stojic and Zusana Jasencakova and Carolina Prezioso and Alexandra St{\"u}tzer and Beatrice Bodega and Diego Pasini and Rebecca Klingberg and Chiara Mozzetta and Raphael Margueron and Puri, {Pier Lorenzo} and Dirk Schwarzer and Kristian Helin and Wolfgang Fischle and Valerio Orlando",

year = "2011",

month = sep,

day = "5",

doi = "10.1186/1756-8935-4-16",

language = "English",

volume = "4",

journal = "Epigenetics and Chromatin",

issn = "1756-8935",

publisher = "BioMed Central Ltd.",

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TY - JOUR

T1 - Chromatin regulated interchange between polycomb repressive complex 2 (PRC2)-Ezh2 and PRC2-Ezh1 complexes controls myogenin activation in skeletal muscle cells

AU - Stojic, Lovorka

AU - Jasencakova, Zusana

AU - Prezioso, Carolina

AU - Stützer, Alexandra

AU - Bodega, Beatrice

AU - Pasini, Diego

AU - Klingberg, Rebecca

AU - Mozzetta, Chiara

AU - Margueron, Raphael

AU - Puri, Pier Lorenzo

AU - Schwarzer, Dirk

AU - Helin, Kristian

AU - Fischle, Wolfgang

AU - Orlando, Valerio

PY - 2011/9/5

Y1 - 2011/9/5

N2 - Background: Polycomb group (PcG) genes code for chromatin multiprotein complexes that are responsible for maintaining gene silencing of transcriptional programs during differentiation and in adult tissues. Despite the large amount of information on PcG function during development and cell identity homeostasis, little is known regarding the dynamics of PcG complexes and their role during terminal differentiation. Results: We show that two distinct polycomb repressive complex (PRC)2 complexes contribute to skeletal muscle cell differentiation: the PRC2-Ezh2 complex, which is bound to the myogenin (MyoG) promoter and muscle creatine kinase (mCK) enhancer in proliferating myoblasts, and the PRC2-Ezh1 complex, which replaces PRC2-Ezh2 on MyoG promoter in post-mitotic myotubes. Interestingly, the opposing dynamics of PRC2-Ezh2 and PRC2-Ezh1 at these muscle regulatory regions is differentially regulated at the chromatin level by Msk1 dependent methyl/phospho switch mechanism involving phosphorylation of serine 28 of the H3 histone (H3S28ph). While Msk1/H3S28ph is critical for the displacement of the PRC2-Ezh2 complex, this pathway does not influence the binding of PRC2-Ezh1 on the chromatin. Importantly, depletion of Ezh1 impairs muscle differentiation and the chromatin recruitment of MyoD to the MyoG promoter in differentiating myotubes. We propose that PRC2-Ezh1 is necessary for controlling the proper timing of MyoG transcriptional activation and thus, in contrast to PRC2-Ezh2, is required for myogenic differentiation. Conclusions: Our data reveal another important layer of epigenetic control orchestrating skeletal muscle cell terminal differentiation, and introduce a novel function of the PRC2-Ezh1 complex in promoter setting.

AB - Background: Polycomb group (PcG) genes code for chromatin multiprotein complexes that are responsible for maintaining gene silencing of transcriptional programs during differentiation and in adult tissues. Despite the large amount of information on PcG function during development and cell identity homeostasis, little is known regarding the dynamics of PcG complexes and their role during terminal differentiation. Results: We show that two distinct polycomb repressive complex (PRC)2 complexes contribute to skeletal muscle cell differentiation: the PRC2-Ezh2 complex, which is bound to the myogenin (MyoG) promoter and muscle creatine kinase (mCK) enhancer in proliferating myoblasts, and the PRC2-Ezh1 complex, which replaces PRC2-Ezh2 on MyoG promoter in post-mitotic myotubes. Interestingly, the opposing dynamics of PRC2-Ezh2 and PRC2-Ezh1 at these muscle regulatory regions is differentially regulated at the chromatin level by Msk1 dependent methyl/phospho switch mechanism involving phosphorylation of serine 28 of the H3 histone (H3S28ph). While Msk1/H3S28ph is critical for the displacement of the PRC2-Ezh2 complex, this pathway does not influence the binding of PRC2-Ezh1 on the chromatin. Importantly, depletion of Ezh1 impairs muscle differentiation and the chromatin recruitment of MyoD to the MyoG promoter in differentiating myotubes. We propose that PRC2-Ezh1 is necessary for controlling the proper timing of MyoG transcriptional activation and thus, in contrast to PRC2-Ezh2, is required for myogenic differentiation. Conclusions: Our data reveal another important layer of epigenetic control orchestrating skeletal muscle cell terminal differentiation, and introduce a novel function of the PRC2-Ezh1 complex in promoter setting.

U2 - 10.1186/1756-8935-4-16

DO - 10.1186/1756-8935-4-16

M3 - Journal article

C2 - 21892963

SN - 1756-8935

VL - 4

JO - Epigenetics and Chromatin

JF - Epigenetics and Chromatin

ER -

Chromatin regulated interchange between polycomb repressive complex 2 (PRC2)-Ezh2 and PRC2-Ezh1 complexes controls myogenin activation in skeletal muscle cells

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