Epigenetic effects induced by the ectopic expression of Pax7 in 3T3-L1

2021 ◽  
Author(s):  
Alaa Elgaabari ◽  
Atsuko Miyawaki-Kuwakado ◽  
Kosuke Tomimatsu ◽  
Qianmei Wu ◽  
Kosuke Tokunaga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Ectopic Expression ◽  
Histone Mark ◽  
Differentiation Potential ◽  
Muscle Gene Expression ◽  
Repressive Histone Mark ◽  
Myogenic Factor ◽  
Muscle Gene

Abstract Although skeletal muscle cells and adipocytes are derived from the same mesoderm, they do not transdifferentiate in vivo and are strictly distinct at the level of gene expression. To elucidate some of the regulatory mechanisms underlying this strict distinction, Pax7, a myogenic factor, was ectopically expressed in 3T3-L1 adipose progenitor cells to perturb their adipocyte differentiation potential. Transcriptome analysis showed that ectopic expression of Pax7 repressed the expression of some adipocyte genes and induced expression of some skeletal muscle cell genes. We next profiled the epigenomic state altered by Pax7 expression using H3K27ac, an activating histone mark, and H3K27me3, a repressive histone mark, as indicators. Our results show that ectopic expression of Pax7 did not result in the formation of H3K27ac at loci of skeletal muscle-related genes, but instead resulted in the formation of H3K27me3 at adipocyte-related gene loci. These findings suggest that the primary function of ectopic Pax7 expression is the formation of H3K27me3, and muscle gene expression results from secondary regulation.

scholarly journals Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245618
Author(s):  
Abhinav Adhikari ◽  
William Kim ◽  
Judith Davie
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Gene Activation ◽  
Gene Promoters ◽  
Muscle Gene Expression ◽  
Transcription Machinery ◽  
Muscle Genes ◽  
Muscle Gene

Skeletal muscle gene expression is governed by the myogenic regulatory family (MRF) which includes MyoD (MYOD1) and myogenin (MYOG). MYOD1 and MYOG are known to regulate an overlapping set of muscle genes, but MYOD1 cannot compensate for the absence of MYOG in vivo. In vitro, late muscle genes have been shown to be bound by both factors, but require MYOG for activation. The molecular basis for this requirement was unclear. We show here that MYOG is required for the recruitment of TBP and RNAPII to muscle gene promoters, indicating that MYOG is essential in assembling the transcription machinery. Genes regulated by MYOD1 and MYOG include genes required for muscle fusion, myomaker and myomerger, and we show that myomaker is fully dependent on activation by MYOG. We also sought to determine the role of MYOD1 in MYOG dependent gene activation and unexpectedly found that MYOG is required to maintain Myod1 expression. However, we also found that exogenous MYOD1 was unable to compensate for the loss of Myog and activate muscle gene expression. Thus, our results show that MYOD1 and MYOG act in a feed forward loop to maintain each other’s expression and also show that it is MYOG, and not MYOD1, that is required to load TBP and activate gene expression on late muscle gene promoters bound by both factors.

scholarly journals Cyclin-mediated inhibition of muscle gene expression via a mechanism that is independent of pRB hyperphosphorylation.

1996 ◽  
Vol 16 (12) ◽  
pp. 7043-7053 ◽  
Author(s):  
S X Skapek ◽  
J Rhee ◽  
P S Kim ◽  
B G Novitch ◽  
A B Lassar
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Cyclin D1 ◽  
Ectopic Expression ◽  
Muscle Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Muscle Gene Expression ◽  
Cell Biol ◽  
Cdk Phosphorylation ◽  
Muscle Gene

It was recently demonstrated that ectopic expression of cyclin D1 inhibits skeletal muscle differentiation and, conversely, that expression of cyclin-dependent kinase (cdk) inhibitors facilitates activation of this differentiation program (S. S. Rao, C. Chu, and D. S. Kohtz, Mol. Cell. Biol. 14:5259-5267, 1994; S. S. Rao and D. S. Kohtz, J. Biol. Chem. 270:4093-4100, 1995; S. X. Skapek, J. Rhee, D. B. Spicer, and A. B. Lassar, Science 267:1022-1024, 1995). Here we demonstrate that cyclin D1 inhibits muscle gene expression without affecting MyoD DNA binding activity. Ectopic expression of cyclin D1 inhibits muscle gene activation by both MyoD and myogenin, including a mutated form of myogenin in which two potential inhibitory cdk phosphorylation sites are absent. Because the retinoblastoma gene product, pRB, is a known target for cyclin D1-cdk phosphorylation, we determined whether cyclin D1-mediated inhibition of myogenesis was due to hyperphosphorylation of pRB. In pRB-deficient fibroblasts, the ability of MyoD to activate the expression of muscle-specific genes requires coexpression of ectopic pRB (B. G. Novitch, G. J. Mulligan, T. Jacks, and A. B. Lassar, J. Cell Biol., 135:441-456, 1996). In these cells, the expression of cyclins A and E can lead to pRB hyperphosphorylation and can inhibit muscle gene expression. The negative effects of cyclins A or E on muscle gene expression are, however, reversed by the presence of a mutated form of pRB which cannot be hyperphosphorylated. In contrast, cyclin D1 can inhibit muscle gene expression in the presence of the nonhyperphosphorylatable form of pRB. On the basis of these results we propose that G1 cyclin-cdk activity blocks the initiation of skeletal muscle differentiation by two distinct mechanisms: one that is dependent on pRB hyperphosphorylation and one that is independent of pRB hyperphosphorylation.

Skeletal muscle gene expression in space‐flown rats

2004 ◽  
Vol 18 (3) ◽  
pp. 522-524 ◽  
Author(s):  
Takeshi Nikawa ◽  
Kazumi Ishidoh ◽  
Katsuya Hirasaka ◽  
Ibuki Ishihara ◽  
Madoka Ikemoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Muscle Gene Expression ◽  
Muscle Gene

Stable incorporation of a bacterial gene into adult rat skeletal muscle in vivo

1990 ◽  
Vol 258 (3) ◽  
pp. C578-C581 ◽  
Author(s):  
D. B. Thomason ◽  
F. W. Booth
Keyword(s):  
Skeletal Muscle ◽  
Leukemia Virus ◽  
Rat Skeletal Muscle ◽  
Bacterial Gene ◽  
Muscle Gene Expression ◽  
Adult Rat ◽  
Foreign Genes ◽  
Muscle Gene ◽  
Beta Galactosidase

We have developed a novel technique to incorporate and stably express foreign genes in adult rat skeletal muscle in vivo. Endogeneous satellite cells in skeletal muscle regenerating from bupivacaine damage were infected with an injected retrovirus containing the Escherichia coli beta-galactosidase gene under the promoter control of the Moloney murine leukemia virus long-terminal repeat. Constitutive and stable expression of beta-galactosidase activity was observed in muscle fibers after 6 days and 1 mo of muscle regeneration. Two patterns of expression were observed, diffuse expression within fibers and focal expression associated with the sarcolemma. This technique will allow future experiments with muscle-specific genes and promoters to study the physiological regulation of skeletal muscle gene expression in the intact adult mammal. Furthermore, the technique of stimulating stem cell proliferation to allow retroviral-mediated gene transfer may be generally applicable to other tissues.

Effects of ractopamine and sex on serum metabolites and skeletal muscle gene expression in finishing steers and heifers

2010 ◽  
Vol 88 (4) ◽  
pp. 1349-1357 ◽  
Author(s):  
D. K. Walker ◽  
E. C. Titgemeyer ◽  
T. J. Baxa ◽  
K. Y. Chung ◽  
D. E. Johnson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Serum Metabolites ◽  
Muscle Gene Expression ◽  
Finishing Steers ◽  
Muscle Gene

scholarly journals Skeletal muscle in aged mice reveals extensive transformation of muscle gene expression

BMC Genetics ◽  
2018 ◽  
Vol 19 (1) ◽  
Author(s):  
I-Hsuan Lin ◽  
Junn-Liang Chang ◽  
Kate Hua ◽  
Wan-Chen Huang ◽  
Ming-Ta Hsu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Aged Mice ◽  
Muscle Gene Expression ◽  
Muscle Gene

Acute endurance exercise stimulates circulating levels of mitochondrial derived peptides in humans

2021 ◽  
Author(s):  
Ferdinand von Walden ◽  
Rodrigo Fernandez-Gonzalo ◽  
Jessica Maria Norrbom ◽  
Eric B. Emanuelsson ◽  
Vandre C. Figueiredo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Diabetes Type 2 ◽  
Knee Extension ◽  
12S Rrna ◽  
Mt Dna ◽  
Reading Frame ◽  
Muscle Gene Expression ◽  
Muscle Gene ◽  
Circulating Levels

Mitochondrial derived peptides (MDPs) humanin (HN) and mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) are involved in cell survival, suppression of apoptosis and metabolism. Circulating levels of MDPs are altered in chronic diseases such as diabetes type 2 and chronic kidney disease. Whether acute resistance (RE) or endurance (EE) exercise modulates circulating levels of HN and MOTS-c in humans is unknown. Following familiarization, subjects were randomized to EE (n=10, 45 min cycling at 70% of estimated VO2max), RE (n=10, 4 sets x 7RM, leg press and knee extension), or control (CON, n=10). Skeletal muscle biopsies and blood samples were collected before and at 30 minutes and 3 hours following exercise. Plasma concentration of HN and MOTS-c, skeletal muscle MOTS-c as well as gene expression of exercise related genes were analyzed. Acute EE and RE promoted changes in skeletal muscle gene expression typically seen in response to each exercise modality (c-Myc, 45S pre-rRNA, PGC-1α-total and PGC-1α-ex1b). At rest, circulating levels of HN were positively correlated to MOTS-c levels and age. Plasma levels of MDPs were not correlated to fitness outcomes (VO2max, leg strength or muscle mitochondrial (mt) DNA copy number). Circulating levels of HN were significantly elevated by acute EE but not RE. MOTS-C levels showed a trend to increase after EE. These results indicate that plasma MDP levels are not related to fitness status but that acute EE increases circulating levels of MDPs, in particular HN.

scholarly journals Skeletal Muscle Gene Expression Study of Monozygous Twins with 35 Years of Divergent Exercise History

2018 ◽  
Vol 50 (5S) ◽  
pp. 115
Author(s):  
Adam Osmond ◽  
Robert J. Talmadge ◽  
Katie E. Bathgate ◽  
James R. Bagley ◽  
Lee E. Brown ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Gene Expression Study ◽  
Expression Study ◽  
Muscle Gene Expression ◽  
Muscle Gene ◽  
Monozygous Twins
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