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From Genetics to Epigenetics: New Perspectives in Tourette Syndrome Research.

Pagliaroli L, Vető B, Arányi T, Barta C - Front Neurosci (2016)

Bottom Line: Epigenetic regulation has been shown to have an impact in the development of many neuropsychiatric disorders, however very little is known about its effects on Tourette Syndrome.Epigenetic studies in other neurological and psychiatric disorders are discussed along with the TS-related epigenetic findings available in the literature to date.Moreover, we are proposing that some general epigenetic mechanisms seen in other neuropsychiatric disorders may also play a role in the pathogenesis of TS.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis UniversityBudapest, Hungary; Research Centre for Natural Sciences, Institute of Enzymology, Hungarian Academy of SciencesBudapest, Hungary.

ABSTRACT
Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder marked by the appearance of multiple involuntary motor and vocal tics. TS presents high comorbidity rates with other disorders such as attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). TS is highly heritable and has a complex polygenic background. However, environmental factors also play a role in the manifestation of symptoms. Different epigenetic mechanisms may represent the link between these two causalities. Epigenetic regulation has been shown to have an impact in the development of many neuropsychiatric disorders, however very little is known about its effects on Tourette Syndrome. This review provides a summary of the recent findings in genetic background of TS, followed by an overview on different epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs in the regulation of gene expression. Epigenetic studies in other neurological and psychiatric disorders are discussed along with the TS-related epigenetic findings available in the literature to date. Moreover, we are proposing that some general epigenetic mechanisms seen in other neuropsychiatric disorders may also play a role in the pathogenesis of TS.

No MeSH data available.


Related in: MedlinePlus

Overview of common covalent epigenetic modifications. A schematic nucleosome and examples of potential epigenetic modifications are shown. The histone octamer is represented in a cylindrical form with one pair of histones H3/H4 indicated. The protruding H3 histone tail and DNA are indicated in orange and purple, respectively. Oppositely, histone and DNA modifications are shown in purple and orange. The functional roles of histone modifications are indicated in colored boxes. The enzyme families catalyzing the modifications are listed in boxes below. The enzymatic links between the different cytosine modifications are shown in the upper right corner of the figure.
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Figure 1: Overview of common covalent epigenetic modifications. A schematic nucleosome and examples of potential epigenetic modifications are shown. The histone octamer is represented in a cylindrical form with one pair of histones H3/H4 indicated. The protruding H3 histone tail and DNA are indicated in orange and purple, respectively. Oppositely, histone and DNA modifications are shown in purple and orange. The functional roles of histone modifications are indicated in colored boxes. The enzyme families catalyzing the modifications are listed in boxes below. The enzymatic links between the different cytosine modifications are shown in the upper right corner of the figure.

Mentions: Cells are reacting to acute and chronic environmental changes by altering their gene expression state, which can be considered as their adaptive reaction. The first step in this adaptive reaction is the modification of the chromatin structure. Chromatin is the macromolecular complex containing DNA and nuclear proteins/histones. The nucleosome is the building unit of chromatin. It consists of two of each of the four core histones (H3, H4, H2A, and H2B) forming an octamer wrapped around twice by DNA (Figure 1). The positively charged N-terminal histone tails are prone to undergo several modifications (acetylation, methylation, phosphorylation, etc.). Similarly, DNA can be methylated. These covalent modifications influence the chromatin structure and lead to changes of the transcriptional state of genes. Even though these changes are dynamic, they can be maintained through cell divisions and from one generation to the next. This mechanism, which does not involve the DNA sequence, but allows the transmission of acquired traits through mitosis and sometimes through a few generations, is called epigenetic inheritance. Another main but chromatin-independent epigenetic mechanism is via non-coding RNAs, which also play a crucial role in gene expression regulation often together with chromatin-related mechanisms.


From Genetics to Epigenetics: New Perspectives in Tourette Syndrome Research.

Pagliaroli L, Vető B, Arányi T, Barta C - Front Neurosci (2016)

Overview of common covalent epigenetic modifications. A schematic nucleosome and examples of potential epigenetic modifications are shown. The histone octamer is represented in a cylindrical form with one pair of histones H3/H4 indicated. The protruding H3 histone tail and DNA are indicated in orange and purple, respectively. Oppositely, histone and DNA modifications are shown in purple and orange. The functional roles of histone modifications are indicated in colored boxes. The enzyme families catalyzing the modifications are listed in boxes below. The enzymatic links between the different cytosine modifications are shown in the upper right corner of the figure.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940402&req=5

Figure 1: Overview of common covalent epigenetic modifications. A schematic nucleosome and examples of potential epigenetic modifications are shown. The histone octamer is represented in a cylindrical form with one pair of histones H3/H4 indicated. The protruding H3 histone tail and DNA are indicated in orange and purple, respectively. Oppositely, histone and DNA modifications are shown in purple and orange. The functional roles of histone modifications are indicated in colored boxes. The enzyme families catalyzing the modifications are listed in boxes below. The enzymatic links between the different cytosine modifications are shown in the upper right corner of the figure.
Mentions: Cells are reacting to acute and chronic environmental changes by altering their gene expression state, which can be considered as their adaptive reaction. The first step in this adaptive reaction is the modification of the chromatin structure. Chromatin is the macromolecular complex containing DNA and nuclear proteins/histones. The nucleosome is the building unit of chromatin. It consists of two of each of the four core histones (H3, H4, H2A, and H2B) forming an octamer wrapped around twice by DNA (Figure 1). The positively charged N-terminal histone tails are prone to undergo several modifications (acetylation, methylation, phosphorylation, etc.). Similarly, DNA can be methylated. These covalent modifications influence the chromatin structure and lead to changes of the transcriptional state of genes. Even though these changes are dynamic, they can be maintained through cell divisions and from one generation to the next. This mechanism, which does not involve the DNA sequence, but allows the transmission of acquired traits through mitosis and sometimes through a few generations, is called epigenetic inheritance. Another main but chromatin-independent epigenetic mechanism is via non-coding RNAs, which also play a crucial role in gene expression regulation often together with chromatin-related mechanisms.

Bottom Line: Epigenetic regulation has been shown to have an impact in the development of many neuropsychiatric disorders, however very little is known about its effects on Tourette Syndrome.Epigenetic studies in other neurological and psychiatric disorders are discussed along with the TS-related epigenetic findings available in the literature to date.Moreover, we are proposing that some general epigenetic mechanisms seen in other neuropsychiatric disorders may also play a role in the pathogenesis of TS.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis UniversityBudapest, Hungary; Research Centre for Natural Sciences, Institute of Enzymology, Hungarian Academy of SciencesBudapest, Hungary.

ABSTRACT
Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder marked by the appearance of multiple involuntary motor and vocal tics. TS presents high comorbidity rates with other disorders such as attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). TS is highly heritable and has a complex polygenic background. However, environmental factors also play a role in the manifestation of symptoms. Different epigenetic mechanisms may represent the link between these two causalities. Epigenetic regulation has been shown to have an impact in the development of many neuropsychiatric disorders, however very little is known about its effects on Tourette Syndrome. This review provides a summary of the recent findings in genetic background of TS, followed by an overview on different epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs in the regulation of gene expression. Epigenetic studies in other neurological and psychiatric disorders are discussed along with the TS-related epigenetic findings available in the literature to date. Moreover, we are proposing that some general epigenetic mechanisms seen in other neuropsychiatric disorders may also play a role in the pathogenesis of TS.

No MeSH data available.


Related in: MedlinePlus