Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD.

Weintraub, Harold; Tapscott, S J; Davis, Robert L.; Thayer, Mathew J.; Adam, Mohammed; Lassar, Andrew B.; Miller, A D

doi:10.1073/pnas.86.14.5434

Cited by 905 publications

(611 citation statements)

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“…ruination geae number 1, MyoDI) [1] considerable interest has been focussed on the analysis of factors which induce myogenesis and the expression of musclespecific structural genes [2]. Other proteins structurally related to MyoD also convert fibroblast (C3H 10TI/2) cells into muscle cells and were named myogenin [3,4] myf-5 [5] and Mrf-4 [6] also known as herculin [7] or myf-6 [8].…”

Section: Introductionmentioning

confidence: 99%

Differential regulation of MyoD and myogenin mRNA levels by nerve induced muscle activity

1991

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The levels or mRNAs coding for the myogenic factors MyoD and myogemn were measured dtlrin8 synapse formation in dry©loping mu~l~ and in adult muscle, after denervation and reinnervatlon ~.nd after muscle paralysis Induced by blocking of n~uromu~cular transmission by neurotosins known to alter the density and localization of s~naptie proteins such as the acetyleholine receptor (AChR), Th~ mRNA levels of both factors d~l~nd on usalle of the neuromuscular synapses, but they change to different extents, Myogenin mRNA levels decrease drastically with inncrva lion and increase strongly following blocking of transmfs~ion whereas the level of MyoD mRNA showed only a small decrease in response to innetvatlon, denervation or muscl© paralysis by neurotoxins, Neither mRNA showed a synapse.related cellular distribution. The results suggest that nerve.induced ©l~trical muscle activity determines the cellular ratio of MyoD and myogenln mRNAs in adult muscle, are also directly involved in the regulation of proteins which are localized at the neuromuscular synapse such as the AChR. We have measured the changes in the levels of MyoD. and myogenic-specific mRNA levels during establishment, maintenance and disruption of neuromuscular transmission, during which there are dramatic changes in the level and spatial distribution of synapse-specific mRNAs and proteins. MATERIALS AND METHODS 2,1. Isolation and surgery of rat muscleTriceps muscles from adult Wistar rats (150-300 g) or rats of various postnatal ages, killed with ether, CO2 or decapitated were removed and immediately frozen in liquid nitrogen, Denervation and reinnervation experiments were performed as described previously [12], Pharmacological muscle inactivation was induced either by injection of botulinum toxin (BoTX) type A into the triceps muscle or by chronic blockade of nerve signal conduction in the sciatic nerve usmg tetrodotoxin (TTX) following procedures described by Brenner et el. [13] [16] to Biodyne membranes (Pall) and crosslinked with the UV Stratalinker from Stratagene. Hybridization was carried out following the procedure recommended by Pall. The membranes were exposed to X.ray film (Kodak X-OMAT) for 1-3 days at -70°C using intensifying screens. 2,3. Hybridization probesHybridization probes were labelled with [a-~aP]dCTP using the random primed labelling kit from Boehringer (Mannheim) F.vt~h~atlon oy uuloratttoxramsEqual Ioad/nj or total RNA wa~ ascertained by czhhltum bromide staining ot the agaro~e lids, The ribosomal 18S and 2~t,~ [~,NA band~ served as internal standards, Loadtnll increasinll amounts (2-I$ all) or total RNA showed a linear increase in ~peeiftg hybridlxation signals, In ~ome ca~es the .~ame blots were rehybrltllzed usin8 AChR ~ubuni~ or acdn mRNA ~pe¢irie probes (Witxemann et al.. in preparation) to conrlrm the specificity of the observed ehan~es in mRNA content (not shown), Autoradiogram5 were ~anned with the dual wavelenlltl~ ~¢anner from Shimadzu (CS.910). For d~ndtomelrie evaluation care was taken to scan autoradioilrams who~e ...

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Section: Introductionmentioning

confidence: 99%

Differential regulation of MyoD and myogenin mRNA levels by nerve induced muscle activity

1991

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“…However, exogenous MyoD in endodermal and ectodermal cells failed to induce a full phenotypic switch (Weintraub et al 1989;Sch€ afer et al 1990). Later studies revealed that MyoD induces myogenin through cooperation with the Pbx factor, which is constitutively bound to MyoD target sites in fibroblasts prior to MyoD expression (Berkes et al 2004).…”

Section: Espinosa and Emerson 2001mentioning

confidence: 99%

Pioneer transcription factors in cell reprogramming

2014

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A subset of eukaryotic transcription factors possesses the remarkable ability to reprogram one type of cell into another. The transcription factors that reprogram cell fate are invariably those that are crucial for the initial cell programming in embryonic development. To elicit cell programming or reprogramming, transcription factors must be able to engage genes that are developmentally silenced and inappropriate for expression in the original cell. Developmentally silenced genes are typically embedded in ''closed'' chromatin that is covered by nucleosomes and not hypersensitive to nuclease probes such as DNase I. Biochemical and genomic studies have shown that transcription factors with the highest reprogramming activity often have the special ability to engage their target sites on nucleosomal DNA, thus behaving as ''pioneer factors'' to initiate events in closed chromatin. Other reprogramming factors appear dependent on pioneer factors for engaging nucleosomes and closed chromatin. However, certain genomic domains in which nucleosomes are occluded by higher-order chromatin structures, such as in heterochromatin, are resistant to pioneer factor binding. Understanding the means by which pioneer factors can engage closed chromatin and how heterochromatin can prevent such binding promises to advance our ability to reprogram cell fates at will and is the topic of this review.Cell fate control represents the most extreme form of gene regulation. Genes specific to the function of a particular type of cell may be antagonistic to the function of another type of cell, so nature has evolved diverse regulatory mechanisms to ensure stable patterns of gene activation and repression. In prokaryotes, self-sustaining regulatory networks of transcription factors bound to DNA can be sufficient to regulate gene activation and repression (Ptashne 2011). In eukaryotes, ;200-base-pair (bp) segments of the genome are wound nearly twice around an octamer of the four core histones to form nucleosomes, providing steric constraints on how transcription factors can bind DNA (Kornberg and Lorch 1999). As described below, pioneer transcription factors have the special property of being able to overcome such constraints, enabling the factors to engage closed chromatin that is not accessible by other types of transcription factors (Fig. 1). However, further higher-order packaging of nucleosomes into heterochromatin can occlude access to DNA altogether, presenting an additional barrier to cell fate conversion (Fig. 1). This review focuses on the most recent studies of pioneer factors in cell programming and reprogramming, how pioneer factors have special chromatinbinding properties, and facilitators and impediments to chromatin binding. We project that such knowledge will greatly aid future efforts to change the fates of cells at will for research, diagnostic, and therapeutic purposes.

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“…Both MyoD and myogenin can program non-muscle cells to myogenic fate and induce differentiation in vitro through a process called myogenic conversion. 52 As discussed earlier, MyoD acts upstream of myogenin and transcriptionally activates myogenin. 8,9,13,14 We anticipated that p53 would repress endogenous myogenin transcription activated by ectopic MyoD and would not repress ectopic myogenin driven by a constitutive promoter.…”

Section: Resultsmentioning

confidence: 85%

p53 suppresses muscle differentiation at the myogenin step in response to genotoxic stress

et al. 2014

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Acute muscle injury and physiological stress from chronic muscle diseases and aging lead to impairment of skeletal muscle function. This raises the question of whether p53, a cellular stress sensor, regulates muscle tissue repair under stress conditions. By investigating muscle differentiation in the presence of genotoxic stress, we discovered that p53 binds directly to the myogenin promoter and represses transcription of myogenin, a member of the MyoD family of transcription factors that plays a critical role in driving terminal muscle differentiation. This reduction of myogenin protein is observed in G1-arrested cells and leads to decreased expression of late but not early differentiation markers. In response to acute genotoxic stress, p53-mediated repression of myogenin reduces post-mitotic nuclear abnormalities in terminally differentiated cells. This study reveals a mechanistic link previously unknown between p53 and muscle differentiation, and suggests new avenues for managing p53-mediated stress responses in chronic muscle diseases or during muscle aging. Cell Death and Differentiation (2015) 22, 560-573; doi:10.1038/cdd.2014; published online 12 December 2014The tumor suppressor p53 promotes cell cycle arrest or apoptosis in response to diverse stress signals such as DNA damage, thus preventing propagation of genetically compromised cells. [1][2][3] Among the diverse functions attributed to p53, a growing body of evidence supports its role in regulation of differentiation and maintenance of cellular function and integrity. 1,[4][5][6][7] For example, p53 represses Nanog to maintain genetic stability of the stem cell pool by promoting differentiation of mouse embryonic stem cells (mESCs) after DNA damage. 6 Skeletal muscle differentiation, a key step during muscle tissue formation, is orchestrated by the MyoD family of myogenic regulatory factors (MRFs). MyoD determines the myogenic lineage, whereas myogenin, a member of the MRF family, functions downstream of MyoD and plays a critical role in driving terminal differentiation as myogenin-null mice show a lethal deficiency of differentiated skeletal muscle. [8][9][10][11][12][13] The dynamic differentiation program of skeletal muscle is characterized by the orderly expression of genes and structural changes that can be recapitulated in vitro, as myogenic cells undergo cell cycle withdrawal and express early and then late differentiation genes with the formation of mononucleated myocytes to elongated multinucleated myotubes. 8,9,14 Under normal unstressed conditions, p53 has been shown to promote muscle differentiation in vitro. [15][16][17][18][19][20] In contrast, under stress-associated conditions such as inflammation, chronic exposure to double-strand DNA breaks, and aging, enhanced p53 activity has been shown to correlate with skeletal muscle atrophy in vivo. [21][22][23][24][25] In addition, it has been shown that p53 and its downstream effectors are required for an inflammatory cytokine-mediated inhibition of myogenic differentiation in vitro. 22 Int...

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Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD.

Cited by 905 publications

References 31 publications

Differential regulation of MyoD and myogenin mRNA levels by nerve induced muscle activity

Differential regulation of MyoD and myogenin mRNA levels by nerve induced muscle activity

Pioneer transcription factors in cell reprogramming

p53 suppresses muscle differentiation at the myogenin step in response to genotoxic stress

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