Abstract
Environmental pressure affects the genotype throughout different epigenetic processes. There is currently ample evidence on the role of epigenetics in developing various mental disorders. A burden of environmental pressure, such as psychological trauma, and its influence on genotype can lead to a variety of psychopathologies. Thus, this study focuses on the epigenetic activity of the complex protein machinery operating on chromatin - the ATP-dependent chromatin remodeling complexes. Although there are several recent studies on the molecular structure, functions, and taxonomy of ATP-dependent chromatin remodeling complexes, the focus of this paper is to highlight the importance of those 'protein machines' in developing psychiatric disorders. Data were obtained from human preclinical and clinical studies. The results of this review indicate an importance of ATP-dependent chromatin remodeling complexes in the interaction between environmental factors, including traumatic events, and genetic vulnerability to stress. Several studies indicate that ATP-dependent chromatin remodeling complexes play a crucial role in the development and consolidation of memory, in neurodevelopmental processes, and in etiology depressive-like behavior. Thus, the activity of those 'protein machines' emerges as a key factor in the pathophysiology of various psychiatric diseases. It can also be concluded that the limitations of clinical studies may be explained by inappropriate laboratory methods and research paradigms due to the delayed timeframe of biochemical responses to environmental stimuli. Future research in this field may enable a better understanding of the pathophysiology of psychiatric diseases and contribute to the development of novel molecular treatment targets.
Highlights
There is a growing body of evidence that epigenetic processes play an important role in the development of psychopathologies
We excluded six of these articles based on the following exclusion criteria: (1) articles concerning strictly molecular structure and/or physicochemical properties of ATP-dependent chromatin remodeling complexes, (2) articles concerning the function of ATPdependent chromatin remodeling complexes outside the nervous system, and (3) articles concerning the role of epigenetic mechanisms other than ATP-dependent chromatin remodeling complexes in the development of mental disorders
There are several human diseases associated with the chromodomain helicase DNA-binding (CHD) protein family and some reports suggest that it has an anticancer properties (Rother and van Attikum, 2017), but due to the scope of this article we focus on the CHD8 gene, which is strongly associated with autism spectrum disorder (ASD)
Summary
There is a growing body of evidence that epigenetic processes play an important role in the development of psychopathologies. The following processes have been recognized as epigenetic mechanisms: DNA methylation, modification of histones (e.g. methylation, acetylation, and phosphorylation), regulation of DNA expression by microRNA species, and modification via ATP-dependent protein complexes. By targeting epigenetics in psychiatry research, several studies have focused on DNA methylation and histone acetylation (Table 1), yet nucleosome remodeling via ATP-dependent complexes in developing psychopathologies remains an unexplored area. These protein complexes control the histone arrangement
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