MyoD induces ARTD1 and nucleoplasmic poly-ADP-ribosylation during fibroblast to myoblast transdifferentiation

Bisceglie, Lavinia; Hopp, Ann-Katrin; Gunasekera, Kapila; Wright, Roni H. G.; Dily, François Le; Vidal, Enrique; Dall’Agnese, Alessandra; Caputo, Luca; Nicoletti, Chiara; Puri, Pier Lorenzo; Beato, Miguel; Hottiger, Michael O.

doi:10.1016/j.isci.2021.102432

Cited by 3 publications

(4 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results establish PAR deposition by PARP1 as well as its auto-PARylation occurring with the first 24hours of myogenic activation. This supports recent work showing PARP1 mediated PAR deposition following MYOD driven transdifferentiation of fibroblasts into myoblasts (31). While the molecular recipients of the differentiating day 1 PAR accumulation are yet to be identified, existing evidence indicates MYOD is a likely target.…”

Section: Parp1 and Parylation Are Dynamic During Skeletal Muscle Myog...supporting

confidence: 88%

“…Further insight into which substrates are PARylated within the first day of myogenesis where PAR disposition is at its highest will be useful in defining downstream signaling. In this regard, nuclear PARP1 mediated PARylating activities are increased in the myoblast following successful transdifferentiation from fibroblasts, providing merit for this (31). It is, however, likely that site-specific PARylation of key myogenic regulators occurs, although this remains to be tested, once performed, it would reveal specific amino acid sequences serving to impact the myogenic protein activity and the continual process of muscle turnover.…”

Section: Parp1 Mediated Parylation Contributes To Myogenesismentioning

confidence: 99%

See 1 more Smart Citation

PARP1 mediated PARylation contributes to myogenic progression and glucocorticoid transcriptional response.

Tan

Younis

Creighton

et al. 2022

Preprint

View full text Add to dashboard Cite

Poly-(ADP-ribose)polymerase 1 (PARP1) enzymatically generates and applies the post-translational modification, as mono (MAR) or poly (PAR) ADP-Ribose (ADPR) chains. PARP1 roles in genome maintenance are well described, but recent work highlight roles in many fundamental processes including cellular identity and energy homeostasis. Herein, we show in both mouse and human skeletal muscle cells that PARP1 mediated PARylation is a regulator of the myogenic program and the muscle transcriptional response to steroid hormones. Chemical PARP1 modulation impacts expression of major myocellular proteins, including troponins, key in dictating muscle contractile force. Whilst PARP1 in absence of DNA damage is often assumed to be basally inactive, we show PARylation to be acutely sensitive to extracellular glucose concentrations and the steroid hormone class, glucocorticoids which exert considerable authority over muscle tissue mass. Specifically, we find during myogenesis, a transient and significant rise in PAR. This early-stage differentiation event, if blocked with PARP1 inhibition, reduced the abundance of important muscle proteins in the fully differentiated myotubes. This suggests that PAR targets during early-stage differentiation are central to the proper development of the muscle contractile unit. We also show that reduced PARP1 in myoblasts impacts a variety of metabolic pathways in line with the recorded actions of glucocorticoids. Currently, as both regulators of myogenesis and muscle mass loss, glucocorticoids represent a clinical conundrum. Our work goes on to identify that PARP1 expression is required for the transcriptional activation by glucocorticoids of a subset of genes critical to human skeletal muscle pathology. These genes may therefore signify a regulatory battery of targets through which selective glucocorticoid modulation could be achieved. Collectively, our data provide clear links between PARP1 mediated PARylation and skeletal muscle homeostatic mechanisms crucial to tissue mass maintenance and endocrine response.

show abstract

Section: Parp1 and Parylation Are Dynamic During Skeletal Muscle Myog...supporting

confidence: 88%

Section: Parp1 Mediated Parylation Contributes To Myogenesismentioning

confidence: 99%

PARP1 mediated PARylation contributes to myogenic progression and glucocorticoid transcriptional response.

Tan

Younis

Creighton

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Additionally, PARP1 and PAR levels are dynamically and differentially regulated in response to exercise between aged untrained and aged trained muscle [ 27 ]. Our results establish PAR deposition by PARP1 as well as its auto-PARylation occurring within the first 24 h of myogenesis, supporting recent work showing PARP1-mediated PAR deposition following MYOD-driven transdifferentiation of fibroblasts into myoblasts [ 28 ]. This increased PAR accumulation could be ascribed to metabolic pathway shifts from glycolysis to oxidative phosphorylation as the major energy source during myogenesis, which has been reported in embryonic stem cells and induced pluripotent stem cells [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…Further insight into which substrates are PARylated within the first day of myogenesis where PAR disposition is at its highest will be useful in defining downstream signaling. In this regard, nuclear PARP1-mediated PARylating activities are increased in the myoblast following successful transdifferentiation from fibroblasts, providing merit for this [ 28 ]. It is, however, likely that site-specific PARylation of key myogenic regulators occurs, although this remains to be tested, once performed, it would reveal specific amino acid sequences serving to impact the myogenic protein activity and the continual process of muscle turnover.…”

Section: Discussionmentioning

confidence: 99%

PARP1 mediated PARylation contributes to myogenic progression and glucocorticoid transcriptional response

et al. 2023

View full text Add to dashboard Cite

The ADP-ribosyltransferase, PARP1 enzymatically generates and applies the post-translational modification, ADP-Ribose (ADPR). PARP1 roles in genome maintenance are well described, but recent work highlights roles in many fundamental processes including cellular identity and energy homeostasis. Herein, we show in both mouse and human skeletal muscle cells that PARP1-mediated PARylation is a regulator of the myogenic program and the muscle transcriptional response to steroid hormones. Chemical PARP1 modulation impacts the expression of major myocellular proteins, including troponins, key in dictating muscle contractile force. Whilst PARP1 in absence of DNA damage is often assumed to be basally inactive, we show PARylation to be acutely sensitive to extracellular glucose concentrations and the steroid hormone class, glucocorticoids which exert considerable authority over muscle tissue mass. Specifically, we find during myogenesis, a transient and significant rise in PAR. This early-stage differentiation event, if blocked with PARP1 inhibition, reduced the abundance of important muscle proteins in the fully differentiated myotubes. This suggests that PAR targets during early-stage differentiation are central to the proper development of the muscle contractile unit. We also show that reduced PARP1 in myoblasts impacts a variety of metabolic pathways in line with the recorded actions of glucocorticoids. Currently, as both regulators of myogenesis and muscle mass loss, glucocorticoids represent a clinical conundrum. Our work goes on to identify that PARP1 influences transcriptional activation by glucocorticoids of a subset of genes critical to human skeletal muscle pathology. These genes may therefore signify a regulatory battery of targets through which selective glucocorticoid modulation could be achieved. Collectively, our data provide clear links between PARP1-mediated PARylation and skeletal muscle homeostatic mechanisms crucial to tissue mass maintenance and endocrine response.

show abstract

Oxidative stress: Roles in skeletal muscle atrophy

Zhang

Wang

et al. 2023

Biochemical Pharmacology

View full text Add to dashboard Cite

MyoD induces ARTD1 and nucleoplasmic poly-ADP-ribosylation during fibroblast to myoblast transdifferentiation

Cited by 3 publications

References 71 publications

PARP1 mediated PARylation contributes to myogenic progression and glucocorticoid transcriptional response.

PARP1 mediated PARylation contributes to myogenic progression and glucocorticoid transcriptional response.

PARP1 mediated PARylation contributes to myogenic progression and glucocorticoid transcriptional response

Oxidative stress: Roles in skeletal muscle atrophy

Contact Info

Product

Resources

About