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At the frontier of epigenetics of brain sex differences.

McCarthy MM, Nugent BM - Front Behav Neurosci (2015)

Bottom Line: The notion that epigenetics may play an important role in the establishment and maintenance of sex differences in the brain has garnered great enthusiasm but the reality in terms of actual advances has been slow.The majority of emphasis has been on candidate genes such as steroid receptors.Only recently have more generalized survey type approaches been achieved and these promise to open new vistas and accelerate discovery of important roles for DNA methylation, histone modification, genomic imprinting and microRNAs (miRs).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Maryland School of Medicine Baltimore, MD, USA.

ABSTRACT
The notion that epigenetics may play an important role in the establishment and maintenance of sex differences in the brain has garnered great enthusiasm but the reality in terms of actual advances has been slow. Two general approaches include the comparison of a particular epigenetic mark in males vs. females and the inhibition of key epigenetic enzymes or co-factors to determine if this eliminates a particular sex difference in brain or behavior. The majority of emphasis has been on candidate genes such as steroid receptors. Only recently have more generalized survey type approaches been achieved and these promise to open new vistas and accelerate discovery of important roles for DNA methylation, histone modification, genomic imprinting and microRNAs (miRs). Technical challenges abound and, while not unique to this field, will require novel thinking and new approaches by behavioral neuroendocrinologists.

No MeSH data available.


Related in: MedlinePlus

Two approaches to epigenetics of brain sex differences. One approach is to simply measure known epigenetic marks such as histone acetylation or CpG methylation, and/or the enzymes known to regulate the establishment and maintenance of these marks and ask, are they different in males and females? A second approach is to disrupt the establishment of epigenetic marks early in development by inhibiting the associated enzymes or cofactors such as methyl binding proteins (MBPs) and ask, does this eliminate sex differences in adult brain and behavior?
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Figure 2: Two approaches to epigenetics of brain sex differences. One approach is to simply measure known epigenetic marks such as histone acetylation or CpG methylation, and/or the enzymes known to regulate the establishment and maintenance of these marks and ask, are they different in males and females? A second approach is to disrupt the establishment of epigenetic marks early in development by inhibiting the associated enzymes or cofactors such as methyl binding proteins (MBPs) and ask, does this eliminate sex differences in adult brain and behavior?

Mentions: There are two general approaches to the study of brain sex differences and epigenetics. The first is to simply measure epigenetic marks in males and females and compare them. The second is to take a known endpoint that is different in males and females, be it morphological or behavioral, and determine if manipulating the system, by blocking or stimulating a key enzyme for instance, disrupts or mimics the formation of the sex differences (Figure 2). Each approach has proven fruitful in its own way. Several recent reviews have effectively cataloged what we currently know and this can be largely summarized as there are sex differences in multiple brain regions in multiple epigenetic marks (Nugent et al., 2010; Nugent and McCarthy, 2011; Auger and Auger, 2013; Kigar and Auger, 2013; Matsuda, 2014). One of the major principles emerging in the larger field of epigenetics is the integral relationship between DNA methylation and histone modifications (Cheng, 2014). Put simply, any change in DNA methylation is likely to be accompanied by some change to the associated histones, and vice versa. But for most investigators analysis is either at the histone or DNA level, unless the work specifically targets this interaction. Yet there is good reason to focus on both, as both types of modifications have been found to either be important for the process of sexual differentiation or changed in response to sexual differentiation. Here are some specifics.


At the frontier of epigenetics of brain sex differences.

McCarthy MM, Nugent BM - Front Behav Neurosci (2015)

Two approaches to epigenetics of brain sex differences. One approach is to simply measure known epigenetic marks such as histone acetylation or CpG methylation, and/or the enzymes known to regulate the establishment and maintenance of these marks and ask, are they different in males and females? A second approach is to disrupt the establishment of epigenetic marks early in development by inhibiting the associated enzymes or cofactors such as methyl binding proteins (MBPs) and ask, does this eliminate sex differences in adult brain and behavior?
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543874&req=5

Figure 2: Two approaches to epigenetics of brain sex differences. One approach is to simply measure known epigenetic marks such as histone acetylation or CpG methylation, and/or the enzymes known to regulate the establishment and maintenance of these marks and ask, are they different in males and females? A second approach is to disrupt the establishment of epigenetic marks early in development by inhibiting the associated enzymes or cofactors such as methyl binding proteins (MBPs) and ask, does this eliminate sex differences in adult brain and behavior?
Mentions: There are two general approaches to the study of brain sex differences and epigenetics. The first is to simply measure epigenetic marks in males and females and compare them. The second is to take a known endpoint that is different in males and females, be it morphological or behavioral, and determine if manipulating the system, by blocking or stimulating a key enzyme for instance, disrupts or mimics the formation of the sex differences (Figure 2). Each approach has proven fruitful in its own way. Several recent reviews have effectively cataloged what we currently know and this can be largely summarized as there are sex differences in multiple brain regions in multiple epigenetic marks (Nugent et al., 2010; Nugent and McCarthy, 2011; Auger and Auger, 2013; Kigar and Auger, 2013; Matsuda, 2014). One of the major principles emerging in the larger field of epigenetics is the integral relationship between DNA methylation and histone modifications (Cheng, 2014). Put simply, any change in DNA methylation is likely to be accompanied by some change to the associated histones, and vice versa. But for most investigators analysis is either at the histone or DNA level, unless the work specifically targets this interaction. Yet there is good reason to focus on both, as both types of modifications have been found to either be important for the process of sexual differentiation or changed in response to sexual differentiation. Here are some specifics.

Bottom Line: The notion that epigenetics may play an important role in the establishment and maintenance of sex differences in the brain has garnered great enthusiasm but the reality in terms of actual advances has been slow.The majority of emphasis has been on candidate genes such as steroid receptors.Only recently have more generalized survey type approaches been achieved and these promise to open new vistas and accelerate discovery of important roles for DNA methylation, histone modification, genomic imprinting and microRNAs (miRs).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Maryland School of Medicine Baltimore, MD, USA.

ABSTRACT
The notion that epigenetics may play an important role in the establishment and maintenance of sex differences in the brain has garnered great enthusiasm but the reality in terms of actual advances has been slow. Two general approaches include the comparison of a particular epigenetic mark in males vs. females and the inhibition of key epigenetic enzymes or co-factors to determine if this eliminates a particular sex difference in brain or behavior. The majority of emphasis has been on candidate genes such as steroid receptors. Only recently have more generalized survey type approaches been achieved and these promise to open new vistas and accelerate discovery of important roles for DNA methylation, histone modification, genomic imprinting and microRNAs (miRs). Technical challenges abound and, while not unique to this field, will require novel thinking and new approaches by behavioral neuroendocrinologists.

No MeSH data available.


Related in: MedlinePlus