Related Experiment Video
Updated: Feb 26, 2026
14:47
Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry
Published on: May 17, 2016
10.3K
BRD3 and BRD4 BET Bromodomain Proteins Differentially Regulate Skeletal Myogenesis
Thomas C Roberts1,2, Usue Etxaniz3, Alessandra Dall'Agnese3
1Sanford Burnham Prebys Medical Discovery Institute, Development, Aging and Regeneration Program, La Jolla, CA, 92037, USA. thomas.roberts@dpag.ox.ac.uk.
Scientific Reports
|July 23, 2017
Summary
Small molecules targeting Bromodomain and Extra Terminal domain (BET) proteins inhibit skeletal muscle development. BRD4 is essential for myogenesis, while BRD3 enhances it, revealing distinct roles for BET proteins.
Area of Science:
- Epigenetics
- Molecular Biology
- Cellular Differentiation
Background:
- Myogenic differentiation involves coordinated gene activation and epigenomic changes.
- Bromodomain and Extra Terminal domain (BET) proteins are epigenetic readers of acetylated histones.
Purpose of the Study:
- To investigate the role of BET proteins in skeletal myogenesis.
- To identify small molecules targeting BET proteins that affect muscle differentiation.
Main Methods:
- Screening of small molecule epigenetic probes.
- Inhibition of myogenic differentiation in C2C12 myoblasts.
- Myogenic conversion assays in human fibroblasts.
- Knockdown of BET proteins using RNA interference.
- Chromatin immunoprecipitation (ChIP) experiments.
Main Results:
- (+)-JQ1, PFI-1, and Bromosporine inhibited myogenic differentiation by targeting BET proteins.
- BET protein expression is regulated post-transcriptionally.
- BRD4 is required for myogenic differentiation, while BRD3 enhances it.
- BRD4 preferentially binds to the Myog promoter during differentiation.
Conclusions:
- BET proteins play essential, distinct roles in regulating skeletal myogenesis.
- BRD4 and BRD3 have opposing functions in muscle differentiation.
Related Concept Videos
02:23Master Transcription Regulators
7.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.9K
01:13Formation of Muscle Fibers from Myoblasts
6.2K
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
6.2K
01:16TGF - β Signaling Pathway
10.7K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.7K
01:21Satellite Stem Cells and Muscular Dystrophy
2.4K
Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...
2.4K
01:23Negative Regulator Molecules
38.7K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.7K
01:30General Transcription Factors
7.3K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
7.3K