The Transcription Elongation Factor A3 (TCEA3) which belongs to the TFIIS family of transcription elongation factors performs a critical role in the regulation of gene transcription. Research confirms that TCEA3 functions as a crucial regulator in myoblast differentiation while enhancing the activity of regulatory myogenic proteins MyoD, Myf5, Myogenin and MRF4. The TCEA3 gene serves as one of three TFIIS family transcription elongation factors present in vertebrate genetic material. During skeletal muscle differentiation TCEA3 expression increases and it stimulates muscle-specific gene activation throughout myogenesis.
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Mechanisms by Transcription Elongation Factor A3 (TCEA3) Promotes Myogenic Regulatory Factors
Increases RNA Polymerase II (Pol II) Transcription Elongation Rates
The function of TCEA3 is to enable RNA Pol II to separate from the DNA template which improves transcription efficiency for target genes. TCEA3 enhances myoblast differentiation during myogenic development by boosting transcription efficiency for critical genes including MyoD and Myogenin.
Works Together With Myod to Drive the Expression of Genes That Control Muscle Development
MyoD functions as a pivotal control unit which directs the process of muscle cell development. By binding to the E-box promoter region this protein enables the expression of genes specific to muscle cells. The research findings reveal that TCEA3 enhances transcription driven by MyoD through its ability to release RNA Pol II from its stalled condition which supports better expression of genes dependent on MyoD.
The Process Enhances Flexible Gene Expression Control Throughout Muscle Cell Development
Early myoblast differentiation stages result in elevated TCEA3 expression levels which, in combination with MyoD and co-activators, activates gene expression linked to myogenesis. This protein functions beyond gene transcription by taking part in chromatin remodeling and epigenetic regulation which establishes a conducive expression environment for myogenic genes.
Fig 1. TCEA3 translocates to the nucleus during differentiation
Mechanism of Transcription Elongation Factor A3 (TCEA3) Regulated by Myogenin
The transcription elongation factor TCEA3 belongs to the TFIIS family and serves as a key player in myoblast differentiation. Myogenin (MyoG) functions as a principal component of the myogenic regulatory factors family by driving the differentiation and maturation processes of muscle cells. Research demonstrates that myogenin controls the expression of TCEA3 while TCEA3 boosts myogenin's transcriptional function which creates a positive feedback loop.
Regulation of Transcription Elongation Factor A3 (TCEA3) by MyoG
Myog Directly Regulates TCEA3 Transcription
The basic helix-loop-helix transcription factor MyoG has specificity for binding to particular E-box (CANNTG) DNA sequences which enables it to drive the transcription of its target genes. MyoG binds directly to the E-box element located in the TCEA3 promoter region during myogenic differentiation to activate transcriptional expression of TCEA3.
Myog Promotes TCEA3 Expression Through Epigenetic Modification
The transcription factor MyoG activates TCEA3 transcription by recruiting histone acetyltransferases like p300/CBP to modify H3K27ac levels in the TCEA3 promoter region. The described mechanism leads to elevated TCEA3 expression during late myogenic differentiation which helps advance muscle cell maturation.
Transcription Elongation Factor A3 (TCEA3) Reversely Promotes Myog Function
TCEA3 Promotes Myog-Dependent Gene Expression
The transcription elongation factor TCEA3 functions to release RNA polymerase II blockages while boosting MyoG target genes expression including MyHC, CKM, and MEF2C. MyoG initially triggers the upregulation of TCEA3 which then boosts MyoG-dependent gene expression resulting in a positive feedback loop.
TCEA3 Promotes Terminal Differentiation of Myoblasts
During the final differentiation stage of myoblasts TCEA3 helps promote MyoG target gene transcription efficiency which in turn speeds up myotube formation. When TCEA3 is inhibited myogenin target genes express at lower levels and myotube formation stops.
Myogenin Directly Regulates Transcription Elongation Factor A3 (TCEA3)
The primary role of myostatin as a negative regulatory factor in skeletal muscle is to prevent muscle growth and development. Research demonstrates myogenin controls muscle cell proliferation and differentiation via several mechanisms. Loss of myogenin resulted in downregulation of Tcea3 during in vivo studies. Activation of Smad2/3 proteins in the myogenin signaling pathway leads to their interaction with transcription factors which likely alters the expression of TCEA3 and other similar transcription factors. Myogenin regulates the expression of downstream genes through control of muscle-specific transcription factors like MyoD and Myogenin.
Transcription Elongation Factor A3 (TCEA3) Promotes Muscle-Specific Gene Expression
The protein TCEA3 serves as a crucial transcription factor binding protein that regulates muscle-specific gene expression. This transcription factor controls genes which govern muscle development and muscle function. TCEA3 stimulates transcription of muscle-specific genes through its interactions with multiple transcription factors and regulatory elements. This factor takes part in cell differentiation and also helps with muscle cell replication while maintaining muscle cell function. TCEA3 supports muscle development and maturation by controlling muscle-specific genes that encode contractile proteins such as actin and troponin. The protein TCEA3 may control signaling pathways that support functions for muscle regeneration and repair. Research indicates that TCEA3 expression level correlates with muscle development and wellness which suggests it could be a future treatment target for muscle illnesses and age-related muscle deterioration. Through the in-depth study of TCEA3 functions and mechanisms scientists aspire to create treatments that enhance muscle health along with functionality.
Transcription Elongation Factor A3 (TCEA3) Promotes Myoblast Differentiation
The TCEA3 protein serves as a fundamental trigger in the development of myoblasts. TCEA3 increases RNA Pol II transcriptional elongation through the activation of myogenic regulatory factors including MyoD and Myogenin. ), thereby accelerating the expression of myogenic genes. Researchers recognize this discovery as a critical advancement in understanding myogenesis molecular mechanisms and its applications in muscle regenerative medicine. Myogenin (MyoG) regulates TCEA3 expression by attaching to its promoter and altering epigenetic modifications. The activity of TCEA3 boosts MyoG-controlled gene transcription through a positive feedback loop to enhance myogenic gene expression. The regulatory mechanism plays a vital role in muscle development and injury repair which makes it a potential new target for muscle regeneration and treatment of muscle diseases.
References
- Guo, Y., et al. Identify Tcea3 as a novel anti-cardiomyocyte hypertrophy gene involved in fatty acid oxidation and oxidative stress. Frontiers in Cardiovascular Medicine. 2023, 10: 1137429.
- Li, J., et al. TCEA3 attenuates gastric cancer growth by apoptosis induction. Medical science monitor: international medical journal of experimental and clinical research. 2015, 21: 3241.
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