Related Experiment Video

Updated: Dec 3, 2025

Epigenetic Regulation of Cardiac Differentiation of Embryonic Stem Cells and Tissues
13:03

Epigenetic Regulation of Cardiac Differentiation of Embryonic Stem Cells and Tissues

Published on: June 3, 2016

8.4K

Epigenetic Reader BRD4 (Bromodomain-Containing Protein 4) Governs Nucleus-Encoded Mitochondrial Transcriptome to

Soo Young Kim1, Xin Zhang2, Gabriele G Schiattarella1

  • 1Division of Cardiology, Department of Internal Medicine (S.Y.K., G.G.S., F.A., K.M.F., N.J., P.A.S., H.I.M., X.L., L.I.S., S.L., T.G.G., J.A.H.), University of Texas Southwestern, Dallas.

Circulation
|October 28, 2020
PubMed

Insights

Bromodomain and extraterminal (BET) protein BRD4 is essential for maintaining normal cardiac function. Loss of BRD4 in cardiomyocytes leads to dilated cardiomyopathy and disrupts mitochondrial energy production, highlighting its critical role in heart health.

Area of Science:

  • Cardiovascular Biology
  • Epigenetics
  • Mitochondrial Physiology

Background:

  • BET proteins, including BRD4, are therapeutic targets for cancer and cardiovascular diseases.
  • Pharmacological inhibitors like JQ1 show promise in preclinical models of heart failure.
  • Genetic validation of BRD4's role in the heart is lacking.

Purpose of the Study:

  • To investigate the function of BRD4 in cardiac pathophysiology using a genetic approach.
  • To elucidate the role of BRD4 in heart development and mature function.
  • To validate findings from pharmacological BET inhibitor studies.

Main Methods:

  • Generated a cardiomyocyte-specific BRD4 knockout mouse model.
  • Performed comprehensive functional, transcriptomic, and mitochondrial analyses.
  • Utilized computational analysis to identify regulatory transcription factors.

Main Results:

  • BRD4 loss caused progressive decline in heart function, leading to dilated cardiomyopathy.
  • Transcriptomic analysis revealed disruption of mitochondrial energy production genes.
  • Mitochondrial studies confirmed altered electron transport chain activity.
  • Estrogen-related receptor α was identified as a key regulator of BRD4-dependent genes.

Conclusions:

  • BRD4 plays a critical, previously unrecognized role in cardiomyocyte mitochondrial homeostasis.
  • BRD4 is indispensable for maintaining normal cardiac function.
  • Genetic ablation of BRD4 has distinct and severe consequences compared to pharmacological inhibition.
Abstract

Keywords:
BRD4 protein, humanelectron transportepigeneticsheart failuremitochondriatranscription, genetic

More Related Videos

Author Spotlight: Nuclei Isolation from Mouse Cardiac Progenitor Cells for Epigenome and Gene Expression Profiling at Single-Cell Resolution10:03

Author Spotlight: Nuclei Isolation from Mouse Cardiac Progenitor Cells for Epigenome and Gene Expression Profiling at Single-Cell Resolution

Published on: May 12, 2023

3.8K
In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge09:53

In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge

Published on: June 15, 2018

7.8K

Related Concept Videos

Master Transcription Regulators02:23

Master Transcription Regulators

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...
7.5K
Animal Mitochondrial Genetics02:59

Animal Mitochondrial Genetics

Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
8.7K
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
7.8K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
15.3K
General Transcription Factors01:30

General Transcription Factors

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...
6.4K
Genomic Imprinting and Inheritance02:30

Genomic Imprinting and Inheritance

Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
36.3K