Six1 Regulates MyoD Expression in Adult Muscle Progenitor Cells

Liu, Yubing; Chakroun, Imane; Yang, Dongfang; Horner, Ellias; Liang, Junquan; Aziz, Arif; Chu, Alphonse; Repentigny, Yves De; Dilworth, F. Jeffrey; Kothary, Rashmi; Blais, Alexandre

doi:10.1371/journal.pone.0067762

Cited by 38 publications

(59 citation statements)

References 56 publications

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“…Eya1 is the coactivator of Six1 (27, 29), and the Six1/Eya1 complex can bind and regulate MyoD expression (30–32). We performed chromatin immunoprecipitation (ChIP) of Six1 and Eya1 at both MyoD and Six1 promoter (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Arginine Methylation by PRMT1 Regulates Muscle Stem Cell Fate

Blanc

Vogel

et al. 2017

Molecular and Cellular Biology

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Quiescent muscle stem cells (MSCs) become activated in response to skeletal muscle injury to initiate regeneration. Activated MSCs proliferate and differentiate to repair damaged fibers or self-renew to maintain the pool and ensure future regeneration. The balance between self-renewal, proliferation, and differentiation is a tightly regulated process controlled by a genetic cascade involving determinant transcription factors such as Pax7, Myf5, MyoD, and MyoG. Recently, there have been several reports about the role of arginine methylation as a requirement for epigenetically mediated control of muscle regeneration. Here we report that the protein arginine methyltransferase 1 (PRMT1) is expressed in MSCs and that conditional ablation of PRMT1 in MSCs using Pax7CreERT2 causes impairment of muscle regeneration. Importantly, PRMT1-deficient MSCs have enhanced cell proliferation after injury but are unable to terminate the myogenic differentiation program, leading to regeneration failure. We identify the coactivator of Six1, Eya1, as a substrate of PRMT1. We show that PRMT1 methylates Eya1 in vitro and that loss of PRMT1 function in vivo prevents Eya1 methylation. Moreover, we observe that PRMT1-deficient MSCs have reduced expression of Eya1/Six1 target MyoD due to disruption of Eya1 recruitment at the MyoD promoter and subsequent Eya1-mediated coactivation. These findings suggest that arginine methylation by PRMT1 regulates muscle stem cell fate through the Eya1/Six1/MyoD axis.

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Section: Resultsmentioning

confidence: 99%

“…4A and B). The latter was used because it is known that Six1 associates with its own promoter (26, 32). Eya1 binding was reduced at MyoD and Six1 genes in the absence of PRMT1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Arginine Methylation by PRMT1 Regulates Muscle Stem Cell Fate

Blanc

Vogel

et al. 2017

Molecular and Cellular Biology

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“…In skeletal muscle, Six1 and Eya1 have been shown to reprogram adult slow-twitch oxidative fibers towards a fast twitch glycolytic 97 and their expression is increased in response to muscle overload 98 . Of note, Six1 is specifically expressed in the satellite cells in skeletal muscle, which are the stem cells within muscle that are important for establishment and regeneration of the tissue 99–101 . In adult mice, a conditional knockout of Six1 in this population of cells demonstrated that Six1 was necessary for proper tissue regeneration and replenishment of the stem cell pool following muscle trauma 99 .…”

Section: Opportunities For Targeting the Six1/eya Transcriptional mentioning

confidence: 99%

The SIX1-EYA transcriptional complex as a therapeutic target in cancer

Blevins

Towers

Patrick

et al. 2015

Expert Opinion on Therapeutic Targets

107

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Introduction The SIX homeodomain proteins and the EYA family of co-activators form a bipartite transcription factor complex that promotes the proliferation and survival of progenitor cells during organogenesis and is down-regulated in most adult tissues. Abnormal over-expression of SIX1 and EYA in adult tissue is associated with the initiation and progression of diverse tumor types. Importantly, SIX1 and EYA are often co-overexpressed in tumors, and the SIX1-EYA2 interaction has been shown to be critical for metastasis in a breast cancer model. The EYA proteins also contain protein tyrosine phosphatase activity, which plays an important role in breast cancer growth and metastasis as well as directing cells to the repair pathway upon DNA damage. Areas covered This review provides a summary of the SIX1/EYA complex as it relates to development and disease and the current efforts to therapeutically target this complex. Expert opinion Recently, there have been an increasing number of studies suggesting that targeting the SIX1/EYA transcriptional complex will potently inhibit tumor progression. Although current attempts to develop inhibitors targeting this complex are still in the early stages, continued efforts towards developing better compounds may ultimately result in effective anti-cancer therapies.

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“…SIX1 expression level is increased in embryogenesis and promotes progenitor cell expansion and survival (6)(7)(8). SIX1 absence results in the reduction in size or loss of numerous organs, as a result of inhibited proliferation and increased apoptosis in mice (9).…”

Section: Introductionmentioning

confidence: 99%

SIX1 is overexpressed in endometrial carcinoma and promotes the malignant behavior of cancer cells through ERK and AKT signaling

Xin

Yang

2016

Oncology Letters

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Abstract. The sineoculis homeobox homolog 1 (SIX1) protein has been found to be important for cancer progression. However, its biological role in human endometrial carcinomas remains unexplored. The potential mechanism of SIX1-induced cancer progression remains unclear. In the present study, SIX1 protein expression was examined in 84 cases of endometrial carcinoma tissues using immunohistochemisty, and SIX1 was found to be overexpressed in 51.1% (43/84) of cervical cancer cells. Small interfering RNA (siRNA) knockdown of SIX1 was also performed in Ishikawa cells with high endogenous SIX1 expression, and SIX1 was overexpressed in the HEC1B cell line with low endogenous expression. SIX1 overexpression promoted cell growth rate and colony formation ability, whereas SIX1 depletion inhibited cell growth and colony formation. Further analysis showed that SIX1 knockdown downregulated, and SIX1 overexpression upregulated, cyclin D1, cyclin E, phosphorylated (p-)extracellular signal-regulated kinase (ERK), and p-protein kinase B (AKT) expression. The ERK inhibitor, U0126, and AKT inhibitor treatments blocked the effect of SIX1 on proliferation. In conclusion, the present study found that SIX1 overexpression promotes cancer cell growth in endometrial carcinoma, possibly through ERK-and AKT-mediated pathways.

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Six1 Regulates MyoD Expression in Adult Muscle Progenitor Cells

Cited by 38 publications

References 56 publications

Arginine Methylation by PRMT1 Regulates Muscle Stem Cell Fate

Arginine Methylation by PRMT1 Regulates Muscle Stem Cell Fate

The SIX1-EYA transcriptional complex as a therapeutic target in cancer

SIX1 is overexpressed in endometrial carcinoma and promotes the malignant behavior of cancer cells through ERK and AKT signaling

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