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Epigenetics and chromatin remodeling in adult cardiomyopathy.

Mahmoud SA, Poizat C - J. Pathol. (2013)

Bottom Line: Histone modifications and ATP-dependent chromatin remodeling together with DNA methylation are dynamic processes that modify chromatin architecture and profoundly modulate gene expression.Their coordinated control is key to ensuring proper cell commitment and organ development, as well as adaption to environmental cues.Understanding the functional significance of the different epigenetic marks as points of genetic control may represent a promising future therapeutic tool.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Research Program, King Faisal Specialist Hospital & Research Centre, PO Box 3354, Riyadh, 11211, Kingdom of Saudi Arabia.

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Schematic representation of epigenetic mechanisms altering chromatin structure and cardiac gene expression. DNA is packaged in chromatin composed of nucleosomes each containing an octamer of histone H3, H4, H2A and H2B. The flexible N-terminal histone “tails” are subjected to post-translational modifications such as acetylation, phosphorylation, methylation and ribosylation. These covalent modifications alter DNA-histone interactions which change chromatin conformation from an “inactive”/repressed state to an “active”/open state, allowing for transcription of cardiac genes. Chromatin conformation can be dynamically regulated by ATP-dependent chromatin remodeling complexes. Changes in DNA methylation can occur in response to stress and contribute to changes in cardiac gene expression.
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fig01: Schematic representation of epigenetic mechanisms altering chromatin structure and cardiac gene expression. DNA is packaged in chromatin composed of nucleosomes each containing an octamer of histone H3, H4, H2A and H2B. The flexible N-terminal histone “tails” are subjected to post-translational modifications such as acetylation, phosphorylation, methylation and ribosylation. These covalent modifications alter DNA-histone interactions which change chromatin conformation from an “inactive”/repressed state to an “active”/open state, allowing for transcription of cardiac genes. Chromatin conformation can be dynamically regulated by ATP-dependent chromatin remodeling complexes. Changes in DNA methylation can occur in response to stress and contribute to changes in cardiac gene expression.

Mentions: Studies from the past two decades have established that local changes in chromatin structure regulate the expression of many eukaryotic genes 23. Chromatin modifications have become integrated into normal gene regulatory pathways. Histones can be modified by post-translational modifications such as acetylation, methylation, phosphorylation and ADP-ribosylation (Figure 1) 4–6. While it is still difficult to decode the specific post-translational modifications at the level of single histones and single nucleosomes, mounting evidence suggests that histone modifications “communicate” and influence one another 23. Epigenomic studies indicate that local changes in chromatin architecture alter specific transcriptional programs and contribute to the development of cardiac pathologies in the adult (Figure 2, Table1).


Epigenetics and chromatin remodeling in adult cardiomyopathy.

Mahmoud SA, Poizat C - J. Pathol. (2013)

Schematic representation of epigenetic mechanisms altering chromatin structure and cardiac gene expression. DNA is packaged in chromatin composed of nucleosomes each containing an octamer of histone H3, H4, H2A and H2B. The flexible N-terminal histone “tails” are subjected to post-translational modifications such as acetylation, phosphorylation, methylation and ribosylation. These covalent modifications alter DNA-histone interactions which change chromatin conformation from an “inactive”/repressed state to an “active”/open state, allowing for transcription of cardiac genes. Chromatin conformation can be dynamically regulated by ATP-dependent chromatin remodeling complexes. Changes in DNA methylation can occur in response to stress and contribute to changes in cardiac gene expression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4285861&req=5

fig01: Schematic representation of epigenetic mechanisms altering chromatin structure and cardiac gene expression. DNA is packaged in chromatin composed of nucleosomes each containing an octamer of histone H3, H4, H2A and H2B. The flexible N-terminal histone “tails” are subjected to post-translational modifications such as acetylation, phosphorylation, methylation and ribosylation. These covalent modifications alter DNA-histone interactions which change chromatin conformation from an “inactive”/repressed state to an “active”/open state, allowing for transcription of cardiac genes. Chromatin conformation can be dynamically regulated by ATP-dependent chromatin remodeling complexes. Changes in DNA methylation can occur in response to stress and contribute to changes in cardiac gene expression.
Mentions: Studies from the past two decades have established that local changes in chromatin structure regulate the expression of many eukaryotic genes 23. Chromatin modifications have become integrated into normal gene regulatory pathways. Histones can be modified by post-translational modifications such as acetylation, methylation, phosphorylation and ADP-ribosylation (Figure 1) 4–6. While it is still difficult to decode the specific post-translational modifications at the level of single histones and single nucleosomes, mounting evidence suggests that histone modifications “communicate” and influence one another 23. Epigenomic studies indicate that local changes in chromatin architecture alter specific transcriptional programs and contribute to the development of cardiac pathologies in the adult (Figure 2, Table1).

Bottom Line: Histone modifications and ATP-dependent chromatin remodeling together with DNA methylation are dynamic processes that modify chromatin architecture and profoundly modulate gene expression.Their coordinated control is key to ensuring proper cell commitment and organ development, as well as adaption to environmental cues.Understanding the functional significance of the different epigenetic marks as points of genetic control may represent a promising future therapeutic tool.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Research Program, King Faisal Specialist Hospital & Research Centre, PO Box 3354, Riyadh, 11211, Kingdom of Saudi Arabia.

Show MeSH
Related in: MedlinePlus