Identification of a Muscle-specific Enhancer within the 5′-Flanking Region of the Human Myoglobin Gene

Devlin, Blythe H.; Wefald, F C; Kraus, William E.; Bernard, Thorens; Williams, R. Sanders

doi:10.1016/s0021-9258(18)80084-9

Cited by 52 publications

(19 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Luciferase reporter plasmids were constructed in pGL3 (Promega) by inserting promoter/enhancer regions from genes encoding human myoglobin (Devlin et al ., 1989) or the SURE and FIRE isoforms of TnIs (Nakayama et al ., 1996). In addition, a synthetic enhancer constructed from three copies of a high affinity MEF2 binding sequence from the desmin promoter [termed desMEF2 (Naya et al ., 1999)] was linked to a minimal promoter (hsp70) and inserted into pGL3.…”

Section: Methodsmentioning

confidence: 99%

MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type

et al. 2000

View full text Add to dashboard Cite

Different patterns of motor nerve activity drive distinctive programs of gene transcription in skeletal muscles, thereby establishing a high degree of metabolic and physiological specialization among myo®ber subtypes. Recently, we proposed that the in¯uence of motor nerve activity on skeletal muscle ®ber type is transduced to the relevant genes by calcineurin, which controls the functional activity of NFAT (nuclear family of activated T cell) proteins. Here we demonstrate that calcineurin-dependent gene regulation in skeletal myocytes is mediated also by MEF2 transcription factors, and is integrated with additional calcium-regulated signaling inputs, speci®cally calmodulin-dependent protein kinase activity. In skeletal muscles of transgenic mice, both NFAT and MEF2 binding sites are necessary for properly regulated function of a slow ®ber-speci®c enhancer, and either forced expression of activated calcineurin or motor nerve stimulation up-regulates a MEF2-dependent reporter gene. These results provide new insights into the molecular mechanisms by which specialized characteristics of skeletal myo®ber subtypes are established and maintained.

show abstract

Section: Methodsmentioning

confidence: 99%

MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type

et al. 2000

View full text Add to dashboard Cite

show abstract

“…In the work of Devlin et al [13] on the human gene, ~2000 nt of 5' sequence was tested for activity. Reducing the size of this tested region did not cause a decrease in activity until they encountered what they termed the myoglobin upstream regulatory element (MbURE), beginning at Hs331 (our numbering; -261 in [13]). Therefore, although distal regulatory elements may exist, available data does not support their presence.…”

Section: Discussion Transcription Driven By Cetacean 5' Flanking Regi...mentioning

confidence: 99%

“…The copyright holder for this preprint (which this version posted April 10, 2023. ; https://doi.org/10.1101/2023.04.10.536305 doi: bioRxiv preprint acutorostrata (Ba). Previous work on regulation of the Hs myoglobin gene identified a muscle-specific core enhancer composed of two sub-regions: an "AT element" and a "CCACbox" [13][14][15]17]. In addition, an isolated E-box, "E-box3" [28] was identified in exon 1.…”

Section: Exploration Of the Minke Whale (Ba) Myoglobin Gene Regulator...mentioning

confidence: 99%

See 1 more Smart Citation

Comparative analysis of myoglobin in Cetaceans and humans reveals novel regulatory elements and evolutionary flexibility

Sackerson

Garcia

Medina

et al. 2023

Preprint

View full text Add to dashboard Cite

Cetacea and other diving mammals have undergone numerous adaptations to their aquatic environment, among them high levels of the oxygen-carrying intracellular hemoprotein myoglobin in skeletal muscles, especially those responsible for swimming. Hypotheses regarding the mechanisms leading to these high myoglobin levels often invoke exercise, hypoxia, and other physiological pathways that impact gene regulation, and increase myoglobin gene expression. Here we explore an alternative hypothesis: that Cetacean myoglobin genes have evolved high levels of transcription driven by the intrinsic developmental mechanisms that drive muscle cell differentiation. We have used luciferase assays in differentiated C2C12 cells to test this hypothesis. Contrary to our hypothesis, we find that the myoglobin gene from the minke whale,Balaenoptera acutorostrata, has a low level of expression, less than 10% that of humans. This low expression level is broadly shared among Cetaceans, and Artiodactylans. Previous work on regulation of the human gene has identified a core muscle-specific enhancer comprised of two regions, the “AT element” and a C-rich sequence 5’ of the AT element termed the “CCAC-box”. Comparative analysis of the minke whale gene supports the importance of the AT element, but the minke whale CCAC-box ortholog has little effect. Instead, critical positive input has been identified in a G-rich region 3’ of the AT element. Also, a conserved E-box in exon 1 positively affects expression, despite having been assigned a repressive role in the human gene. Last, a novel region 5’ of the core enhancer has been identified, which we hypothesize may function as a boundary element. These results illustrate regulatory flexibility during evolution. They also support the hypothesis that the induction of transcription by physiological signaling pathways, and evolved protein stability are important in leading to the high myoglobin protein levels found in Cetaceans.

show abstract

“…The observation of the differential expression pattern of Mb during myogenesis and in various adult striated muscle-fiber types has prompted investigators to study the putative myoglobin promoters and the various transcription factors that are responsible for the regulation of Mb transcription. Using cultured adult myoblasts obtained from 11 to 12-day-old chicken embryonic pectoral muscle, researchers have demonstrated that a 167 bp myoglobin promoter region (−371 to −205), containing a 57 bp cis-acting element, enhanced reporter activity in differentiated myotubes and concluded that the 2 kb putative Mb promoter region contains a muscle-specific enhancer region that is essential for the regulation of Mb transcription during skeletal muscle cell differentiation [ 20 ]. So far, porcine Mb gene has not been identified in the reference genome, and its transcriptional regulation pattern has not been studied, due to the lack of sequence information of the promoter region [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Prediction and Experimental Verification of a Hierarchical Transcription Factor Regulatory Network of Porcine Myoglobin (Mb)

Yuan

Liu

et al. 2021

Animals

View full text Add to dashboard Cite

Myoglobin is a key chemical component that determines meat’s color and affects consumers’ purchase intentions. In this work, we firstly identified the promoter sequence of the Mb gene from the primary assembly of high-throughput genome sequencing in pigs, and predicted its potential transcription factors by LASAGNA. Through the data mining of the mRNA expression profile of longissimus dorsi muscle of different pig breeds, we constructed a hierarchical interplay network of Mb-TFs (Myoglobin-Transcription Factors), consisting of 16 adaptive transcription factors and 23 secondary transcription factors. The verification of gene expression in longissimus dorsi muscle showed that the Mb mRNA and encoded protein were significantly (p < 0.05) more abundant in Bama pigs than Yorkshire pigs. The qRT-PCR (Real-Time Quantitative Reverse Transcription PCR) validation on genes of the Mb-TFs network showed that FOS, STAT3, STAT1, NEFL21, NFE2L2 and MAFB were significant positive regulatory core transcription factors of Mb-TFs network in Bama pigs, whereas ATF3 was the secondary transcription factor most responsible for the activation of the above transcription factors. Our study provides a new strategy to unravel the mechanism of pork color formation, based on public transcriptome and genome data analysis.

show abstract

Identification of a Muscle-specific Enhancer within the 5′-Flanking Region of the Human Myoglobin Gene

Cited by 52 publications

References 35 publications

MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type

MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type

Comparative analysis of myoglobin in Cetaceans and humans reveals novel regulatory elements and evolutionary flexibility

Prediction and Experimental Verification of a Hierarchical Transcription Factor Regulatory Network of Porcine Myoglobin (Mb)

Contact Info

Product

Resources

About