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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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Epigenetic changes in cardiomyopathy. Epigenetic mechanisms such as DNA methylation, histone modifications and ATP-dependent chromatin remodeling alter chromatin structure and modulate gene expression. Histone acetylation by p300/CBP histone acetyltransferases (HATs) changes nucleosome conformation and increases accessibility of transcription factors, resulting in relief of transcriptional repression. Histone deacetylases (HDACs) have the opposite effect and are usually involved in gene repression. Both HATs and HDACs play a role in cardiac hypertrophy. Histone methylation is associated with activation or repression of transcription depending on the residue and the degree of methylation. The functional outcomes of histone methylation and the action of histone demethylases on cardiac gene transcription are shown. Chromatin remodelers such as Brg1 use the energy of ATP to change chromatin structure. These different epigenetic mechanisms are reversible and act in concert to regulate cardiac transcription. Dysregulation of these processes can result in cardiac abnormalities. HDAC4/5/9: histone deacetylases 4,5,9; CBP/p300: histone acetyltransferases; PTIP: PAX interacting protein 1; UTX: histone H3K27 demethylase; JMJD2A: jumonji C domain containing histone demethylase; DOT1L: histone H3 methyltransferase; Brg1: brahma-related gene 1; PARP-1: poly(ADP-ribose) polymerase 1; RNAPII: RNA polymerase II; CaMKII: calcium/calmodulin-dependent protein kinase II; PKD: protein kinase D.
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fig02: Epigenetic changes in cardiomyopathy. Epigenetic mechanisms such as DNA methylation, histone modifications and ATP-dependent chromatin remodeling alter chromatin structure and modulate gene expression. Histone acetylation by p300/CBP histone acetyltransferases (HATs) changes nucleosome conformation and increases accessibility of transcription factors, resulting in relief of transcriptional repression. Histone deacetylases (HDACs) have the opposite effect and are usually involved in gene repression. Both HATs and HDACs play a role in cardiac hypertrophy. Histone methylation is associated with activation or repression of transcription depending on the residue and the degree of methylation. The functional outcomes of histone methylation and the action of histone demethylases on cardiac gene transcription are shown. Chromatin remodelers such as Brg1 use the energy of ATP to change chromatin structure. These different epigenetic mechanisms are reversible and act in concert to regulate cardiac transcription. Dysregulation of these processes can result in cardiac abnormalities. HDAC4/5/9: histone deacetylases 4,5,9; CBP/p300: histone acetyltransferases; PTIP: PAX interacting protein 1; UTX: histone H3K27 demethylase; JMJD2A: jumonji C domain containing histone demethylase; DOT1L: histone H3 methyltransferase; Brg1: brahma-related gene 1; PARP-1: poly(ADP-ribose) polymerase 1; RNAPII: RNA polymerase II; CaMKII: calcium/calmodulin-dependent protein kinase II; PKD: protein kinase D.

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)

Epigenetic changes in cardiomyopathy. Epigenetic mechanisms such as DNA methylation, histone modifications and ATP-dependent chromatin remodeling alter chromatin structure and modulate gene expression. Histone acetylation by p300/CBP histone acetyltransferases (HATs) changes nucleosome conformation and increases accessibility of transcription factors, resulting in relief of transcriptional repression. Histone deacetylases (HDACs) have the opposite effect and are usually involved in gene repression. Both HATs and HDACs play a role in cardiac hypertrophy. Histone methylation is associated with activation or repression of transcription depending on the residue and the degree of methylation. The functional outcomes of histone methylation and the action of histone demethylases on cardiac gene transcription are shown. Chromatin remodelers such as Brg1 use the energy of ATP to change chromatin structure. These different epigenetic mechanisms are reversible and act in concert to regulate cardiac transcription. Dysregulation of these processes can result in cardiac abnormalities. HDAC4/5/9: histone deacetylases 4,5,9; CBP/p300: histone acetyltransferases; PTIP: PAX interacting protein 1; UTX: histone H3K27 demethylase; JMJD2A: jumonji C domain containing histone demethylase; DOT1L: histone H3 methyltransferase; Brg1: brahma-related gene 1; PARP-1: poly(ADP-ribose) polymerase 1; RNAPII: RNA polymerase II; CaMKII: calcium/calmodulin-dependent protein kinase II; PKD: protein kinase D.
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fig02: Epigenetic changes in cardiomyopathy. Epigenetic mechanisms such as DNA methylation, histone modifications and ATP-dependent chromatin remodeling alter chromatin structure and modulate gene expression. Histone acetylation by p300/CBP histone acetyltransferases (HATs) changes nucleosome conformation and increases accessibility of transcription factors, resulting in relief of transcriptional repression. Histone deacetylases (HDACs) have the opposite effect and are usually involved in gene repression. Both HATs and HDACs play a role in cardiac hypertrophy. Histone methylation is associated with activation or repression of transcription depending on the residue and the degree of methylation. The functional outcomes of histone methylation and the action of histone demethylases on cardiac gene transcription are shown. Chromatin remodelers such as Brg1 use the energy of ATP to change chromatin structure. These different epigenetic mechanisms are reversible and act in concert to regulate cardiac transcription. Dysregulation of these processes can result in cardiac abnormalities. HDAC4/5/9: histone deacetylases 4,5,9; CBP/p300: histone acetyltransferases; PTIP: PAX interacting protein 1; UTX: histone H3K27 demethylase; JMJD2A: jumonji C domain containing histone demethylase; DOT1L: histone H3 methyltransferase; Brg1: brahma-related gene 1; PARP-1: poly(ADP-ribose) polymerase 1; RNAPII: RNA polymerase II; CaMKII: calcium/calmodulin-dependent protein kinase II; PKD: protein kinase D.
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