scholarly journals A BAC transgenic analysis of the Mrf4/Myf5 locus reveals interdigitated elements that control activation and maintenance of gene expression during muscle development

Development ◽  
2001 ◽  
Vol 128 (10) ◽  
pp. 1857-1868 ◽  
Author(s):  
J.J. Carvajal ◽  
D. Cox ◽  
D. Summerbell ◽  
P.W. Rigby
Keyword(s):  
Muscle Development ◽  
Expression Patterns ◽  
Artificial Chromosome ◽  
Myogenic Regulatory Factors ◽  
Evolutionary Origins ◽  
Branchial Arches ◽  
Vertebrate Embryo ◽  
Neighbouring Gene ◽  
Complex Regulation ◽  
Control Activation

The muscle-specific transcription factors Myf5 and Mrf4 are two of the four myogenic regulatory factors involved in the transcriptional cascade responsible for skeletal myogenesis in the vertebrate embryo. Myf5 is the first of these four genes to be expressed in the mouse. We have previously described discrete enhancers that drive Myf5 expression in epaxial and hypaxial somites, branchial arches and central nervous system, and argued that additional elements are required for proper expression (Summerbell, D., Ashby, P. R., Coutelle, O., Cox, D., Yee, S. P. and Rigby, P. W. J. (2000) Development 127, 3745–3757). We have now investigated the transcriptional regulation of both Myf5 and Mrf4 using bacterial artificial chromosome transgenesis. We show that a clone containing Myf5 and 140 kb of upstream sequences is sufficient to recapitulate the known expression patterns of both genes. Our results confirm and reinforce the conclusion of our earlier studies, that Myf5 expression is regulated differently in each of a considerable number of populations of muscle progenitors, and they begin to illuminate the evolutionary origins of this complex regulation. We further show that separate elements are involved in the activation and maintenance of expression in the various precursor populations, reflecting the diversity of the signals that control myogenesis. Mrf4 expression requires at least four elements, one of which may be shared with Myf5, providing a possible explanation for the linkage of these genes throughout vertebrate phylogeny. Further complexity is revealed by the demonstration that elements which control Mrf4 and Myf5 are embedded in an unrelated neighbouring gene.

scholarly journals Histone deacetylase (HDAC) 9: versatile biological functions and emerging roles in human cancer

2021 ◽  
Author(s):  
Chun Yang ◽  
Stéphane Croteau ◽  
Pierre Hardy
Keyword(s):  
Histone Deacetylase ◽  
Posttranslational Modifications ◽  
Histone Deacetylases ◽  
Muscle Development ◽  
Target Genes ◽  
Human Cancer ◽  
Expression Patterns ◽  
Aberrant Expression ◽  
Physiological Processes ◽  
Cancer Pathogenesis

Abstract Background HDAC9 (histone deacetylase 9) belongs to the class IIa family of histone deacetylases. This enzyme can shuttle freely between the nucleus and cytoplasm and promotes tissue-specific transcriptional regulation by interacting with histone and non-histone substrates. HDAC9 plays an essential role in diverse physiological processes including cardiac muscle development, bone formation, adipocyte differentiation and innate immunity. HDAC9 inhibition or activation is therefore a promising avenue for therapeutic intervention in several diseases. HDAC9 overexpression is also common in cancer cells, where HDAC9 alters the expression and activity of numerous relevant proteins involved in carcinogenesis. Conclusions This review summarizes the most recent discoveries regarding HDAC9 as a crucial regulator of specific physiological systems and, more importantly, highlights the diverse spectrum of HDAC9-mediated posttranslational modifications and their contributions to cancer pathogenesis. HDAC9 is a potential novel therapeutic target, and the restoration of aberrant expression patterns observed among HDAC9 target genes and their related signaling pathways may provide opportunities to the design of novel anticancer therapeutic strategies.

scholarly journals Transcriptome Analysis of Differentially Expressed mRNA Related to Pigeon Muscle Development

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2311
Author(s):  
Hao Ding ◽  
Yueyue Lin ◽  
Tao Zhang ◽  
Lan Chen ◽  
Genxi Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Differentially Expressed Genes ◽  
Growth And Development ◽  
Muscle Development ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Growth Stages ◽  
Gene Expression And Regulation

The mechanisms behind the gene expression and regulation that modulate the development and growth of pigeon skeletal muscle remain largely unknown. In this study, we performed gene expression analysis on skeletal muscle samples at different developmental and growth stages using RNA sequencing (RNA−Seq). The differentially expressed genes (DEGs) were identified using edgeR software. Weighted gene co−expression network analysis (WGCNA) was used to identify the gene modules related to the growth and development of pigeon skeletal muscle based on DEGs. A total of 11,311 DEGs were identified. WGCNA aggregated 11,311 DEGs into 12 modules. Black and brown modules were significantly correlated with the 1st and 10th day of skeletal muscle growth, while turquoise and cyan modules were significantly correlated with the 8th and 13th days of skeletal muscle embryonic development. Four mRNA−mRNA regulatory networks corresponding to the four significant modules were constructed and visualised using Cytoscape software. Twenty candidate mRNAs were identified based on their connectivity degrees in the networks, including Abca8b, TCONS−00004461, VWF, OGDH, TGIF1, DKK3, Gfpt1 and RFC5, etc. A KEGG pathway enrichment analysis showed that many pathways were related to the growth and development of pigeon skeletal muscle, including PI3K/AKT/mTOR, AMPK, FAK, and thyroid hormone pathways. Five differentially expressed genes (LAST2, MYPN, DKK3, B4GALT6 and OGDH) in the network were selected, and their expression patterns were quantified by qRT−PCR. The results were consistent with our sequencing results. These findings could enhance our understanding of the gene expression and regulation in the development and growth of pigeon muscle.

511 Temporal Expression Patterns of Twelve Genes during Fetal and Postnatal Skeletal Muscle Development in Pigs.

2018 ◽  
Vol 96 (suppl_2) ◽  
pp. 272-273
Author(s):  
B A Wolfer ◽  
K R Daza ◽  
D Velez-Irizarry ◽  
N E Raney ◽  
V D Rilington ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Expression Patterns ◽  
Skeletal Muscle Development ◽  
Temporal Expression

Overlapping functions of the myogenic bHLH genes MRF4 and MyoD revealed in double mutant mice

Development ◽  
1998 ◽  
Vol 125 (13) ◽  
pp. 2349-2358 ◽  
Author(s):  
A. Rawls ◽  
M.R. Valdez ◽  
W. Zhang ◽  
J. Richardson ◽  
W.H. Klein ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Double Mutant ◽  
Muscle Development ◽  
Expression Patterns ◽  
Muscle Fibers ◽  
Mutant Mice ◽  
Myoblast Differentiation ◽  
Bhlh Genes ◽  
Bhlh Factors

The myogenic basic helix-loop-helix (bHLH) genes - MyoD, Myf5, myogenin and MRF4 - exhibit distinct, but overlapping expression patterns during development of the skeletal muscle lineage and loss-of-function mutations in these genes result in different effects on muscle development. MyoD and Myf5 have been shown to act early in the myogenic lineage to establish myoblast identity, whereas myogenin acts later to control myoblast differentiation. In mice lacking myogenin, there is a severe deficiency of skeletal muscle, but some residual muscle fibers are present in mutant mice at birth. Mice lacking MRF4 are viable and have skeletal muscle, but they upregulate myogenin expression, which could potentially compensate for the absence of MRF4. Previous studies in which Myf5 and MRF4 null mutations were combined suggested that these genes do not share overlapping myogenic functions in vivo. To determine whether the functions of MRF4 might overlap with those of myogenin or MyoD, we generated double mutant mice lacking MRF4 and either myogenin or MyoD. MRF4/myogenin double mutant mice contained a comparable number of residual muscle fibers to mice lacking myogenin alone and myoblasts from those double mutant mice formed differentiated multinucleated myotubes in vitro as efficiently as wild-type myoblasts, indicating that neither myogenin nor MRF4 is absolutely essential for myoblast differentiation. Whereas mice lacking either MRF4 or MyoD were viable and did not show defects in muscle development, MRF4/MyoD double mutants displayed a severe muscle deficiency similar to that in myogenin mutants. Myogenin was expressed in MRF4/MyoD double mutants, indicating that myogenin is insufficient to support normal myogenesis in vivo. These results reveal unanticipated compensatory roles for MRF4 and MyoD in the muscle differentiation pathway and suggest that a threshold level of myogenic bHLH factors is required to activate muscle structural genes, with this level normally being achieved by combinations of multiple myogenic bHLH factors.

scholarly journals Neudesin Neurotrophic Factor Promotes Bovine Preadipocyte Differentiation and Inhibits Myoblast Myogenesis

Animals ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1109 ◽  
Author(s):  
Xiaotong Su ◽  
Yaning Wang ◽  
Anqi Li ◽  
Linsen Zan ◽  
Hongbao Wang
Keyword(s):  
Adipose Tissue ◽  
Protein Expression ◽  
Mrna Expression ◽  
Neurotrophic Factor ◽  
Muscle Development ◽  
Expression Patterns ◽  
Marker Genes ◽  
Qinchuan Cattle ◽  
Preadipocyte Differentiation ◽  
Expression Levels

Neudesin neurotrophic factor (NENF) is a secreted protein that is essential in multiple biological processes, including neural functions, adipogenesis, and tumorigenesis. In our previous study, NENF was significantly inhibited in the bovine adipocytes-myoblasts co-culture system. However, studies on NENF regulation of bovine muscle development and involvement in the cross-talk between adipose tissue and skeletal muscle have not been reported. Hence, the aim of this study was to clarify the functional roles of NENF in bovine preadipocytes and myoblasts. Real-time quantitative PCR (RT-qPCR) was performed to examine the spatial expression patterns of NENF in different tissues, and the results showed that NENF was highly expressed in the muscle of four-day-old and 24-month-old Qinchuan cattle. Compared with four-day-old Qinchuan cattle, the expression level of NENF was significantly up-regulated in 24-month-old bovine adipose tissue. To explore the roles of NENF in bovine myoblast and preadipocyte differentiation, small interfering RNA (siRNA) targeting the NENF gene were transfected into bovine preadipocytes and myoblasts to knock down the expression of the NENF gene. The results showed that the knockdown of NENF in differentiating adipocytes attenuated lipid accumulation, decreased the mRNA expression of adipogenic key marker genes PPARγ, CEBPα, CEBPβ, FASN, and SCD1, and decreased the protein expression of PPARγ, CEBPα, and FASN. The formation of myotubes was significantly accelerated, and the mRNA expression levels of myogenic marker genes MYOD1, MYF5, MYF6, MEF2A, MEF2C, and CKM, and the protein expression levels of MYOD1, MYF6, MEF2A, and CKM were up-regulated in myoblasts where NENF was knocked down. In short, the knockdown of NENF inhibited preadipocyte differentiation and promoted myoblast myogenesis.

scholarly journals Age and Sex-Dependent ADNP Regulation of Muscle Gene Expression Is Correlated with Motor Behavior: Possible Feedback Mechanism with PACAP

2020 ◽  
Vol 21 (18) ◽  
pp. 6715 ◽  
Author(s):  
Oxana Kapitansky ◽  
Shlomo Sragovich ◽  
Iman Jaljuli ◽  
Adva Hadar ◽  
Eliezer Giladi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Muscle Development ◽  
Motor Behavior ◽  
Expression Patterns ◽  
Feedback Mechanism ◽  
Bladder Function ◽  
Drug Candidate ◽  
Specific Gene ◽  
Muscle Gene Expression ◽  
Muscle Gene

The activity-dependent neuroprotective protein (ADNP), a double-edged sword, sex-dependently regulates multiple genes and was previously associated with the control of early muscle development and aging. Here we aimed to decipher the involvement of ADNP in versatile muscle gene expression patterns in correlation with motor function throughout life. Using quantitative RT-PCR we showed that Adnp+/− heterozygous deficiency in mice resulted in aberrant gastrocnemius (GC) muscle, tongue and bladder gene expression, which was corrected by the Adnp snippet, drug candidate, NAP (CP201). A significant sexual dichotomy was discovered, coupled to muscle and age-specific gene regulation. As such, Adnp was shown to regulate myosin light chain (Myl) in the gastrocnemius (GC) muscle, the language acquisition gene forkhead box protein P2 (Foxp2) in the tongue and the pituitary-adenylate cyclase activating polypeptide (PACAP) receptor PAC1 mRNA (Adcyap1r1) in the bladder, with PACAP linked to bladder function. A tight age regulation was observed, coupled to an extensive correlation to muscle function (gait analysis), placing ADNP as a muscle-regulating gene/protein.

scholarly journals Conserved transcriptomic profiles underpin monogamy across vertebrates

2019 ◽  
Vol 116 (4) ◽  
pp. 1331-1336 ◽  
Author(s):  
Rebecca L. Young ◽  
Michael H. Ferkin ◽  
Nina F. Ockendon-Powell ◽  
Veronica N. Orr ◽  
Steven M. Phelps ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mating Systems ◽  
Expression Patterns ◽  
Divergence Time ◽  
Brain Regions ◽  
Evolutionary Divergence ◽  
Social Monogamy ◽  
Evolutionary Origins ◽  
Species Pairs ◽  
Genomic Scale

Social monogamy, typically characterized by the formation of a pair bond, increased territorial defense, and often biparental care, has independently evolved multiple times in animals. Despite the independent evolutionary origins of monogamous mating systems, several homologous brain regions and neuropeptides and their receptors have been shown to play a conserved role in regulating social affiliation and parental care, but little is known about the neuromolecular mechanisms underlying monogamy on a genomic scale. Here, we compare neural transcriptomes of reproductive males in monogamous and nonmonogamous species pairs ofPeromyscusmice,Microtusvoles, parid songbirds, dendrobatid frogs, andXenotilapiaspecies of cichlid fishes. We find that, while evolutionary divergence time between species or clades did not explain gene expression similarity, characteristics of the mating system correlated with neural gene expression patterns, and neural gene expression varied concordantly across vertebrates when species transition to monogamy. Our study provides evidence of a universal transcriptomic mechanism underlying the evolution of monogamy in vertebrates.

The relationships of collagen and ADAMTS2 expressionlevels with meat quality traits in cattle

2016 ◽  
Author(s):  
X. H. Zhang ◽  
H. .Liao ◽  
Y. X. Qi ◽  
Y. Q. Wang ◽  
Y. Z. Pang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Meat Quality ◽  
Muscle Development ◽  
Expression Patterns ◽  
Subcutaneous Fat ◽  
Biceps Femoris ◽  
Longissimus Dorsi ◽  
Expression Levels ◽  
Longissimus Dorsi Muscle ◽  
Dorsi Muscle

Extracellular matrix (ECM) is the major macromolecule in skeletal muscle, and collagen is main component of ECM surrounding muscle fiber and adipocyte, which affect meat quality greatly. The remodeling of ECM is regulated by matrix metalloproteinases, such as ADAMTS2, which is essential for the maturation of triple helical collagen fibrils in body. The expression patterns of COL1A1, COL2A1, COL3A1 and ADAMTS2 in longissimus dorsi muscle were explored by qRT-PCR and results indicated that the expression levels of COL1A1, COL3A1 and ADAMTS2 were significantly higher at 3 and 24 month, while significantly lower at 12 and 30 month. The expression of ADAMTS2 and COL1A1 had significant positive relationships with intramuscular fat content, while expression of COL3A1 had significant positive relationship with shearing force and water holding capacity in cattle. The expression levels of collagen and ADAMTS2 were significantly higher in mesenteric fat, mammary fat pad and subcutaneous fat than in longissimus dorsi muscle, biceps femoris and infraspinitus tissues. The expressions levels of COL1A1, COL3A1 and ADAMTS2 were significantly lower in marbling fat than in other fat tissues. This study indicated that the expression of collagen and ADAMTS2 had important effects on postnatal skeletal muscle development and meat quality.

scholarly journals Six4, a Putative myogeninGene Regulator, Is Not Essential for Mouse Embryonal Development

2001 ◽  
Vol 21 (10) ◽  
pp. 3343-3350 ◽  
Author(s):  
Hidenori Ozaki ◽  
Yoko Watanabe ◽  
Katsumasa Takahashi ◽  
Ken Kitamura ◽  
Akira Tanaka ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Dorsal Root ◽  
Skeletal Muscles ◽  
Early Stage ◽  
Expression Patterns ◽  
Homologous Region ◽  
Specific Expression ◽  
Sine Oculis ◽  
Branchial Arches ◽  
Deficient Mice

ABSTRACT Six4 is a member of the Six family genes, homologues of Drosophila melanogaster sine oculis. The gene is thought to be involved in neurogenesis, myogenesis, and development of other organs, based on its specific expression in certain neuronal cells of the developing embryo and in adult skeletal muscles. To elucidate the biological roles of Six4, we generatedSix4-deficient mice by replacing the Sixhomologous region and homeobox by the β-galactosidase gene. 5-Bromo-4-chloro-3-indolyl-β-d-galactopyranoside staining of the heterozygous mutant embryos revealed expression ofSix4 in cranial and dorsal root ganglia, somites, otic and nasal placodes, branchial arches, Rathke's pouch, apical ectodermal ridges of limb buds, and mesonephros. The expression pattern was similar to that of Six1 except at the early stage of embryonic day 8.5. Six4-deficient mice were born according to the Mendelian rule with normal gross appearance and were fertile. No hearing defects were detected. Six4-deficient embryos showed no morphological abnormalities, and the expression patterns of several molecular markers, e.g., myogenin andNeuroD3 (neurogenin1), were normal. Our results indicate that Six4 is not essential for mouse embryogenesis and suggest that other members of the Six family seem to compensate for the loss of Six4.

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