Chromatin Remodeling: An Essay on Biology, Function, and Diseases

This essay provides a comprehensive overview of chromatin remodeling, a fundamental process in eukaryotic cells that controls gene expression by altering the structure of chromatin, a complex of DNA and proteins. The essay details the role of chromatin remodelers, specific molecules that modify chromatin structure, enabling or inhibiting transcription. It explores various mechanisms of chromatin remodeling in different organisms, including the involvement of complexes like SWI/SNF and RSC. The essay also highlights the clinical significance of chromatin remodeling, particularly its association with diseases like Parkinson's disease, where altered DNA methylation and chromatin environment contribute to disease pathogenesis. The essay also covers the function of chromatin remodelers, the structure and function of the different remodeling complexes differ with each other as per their presence in different organisms.

Running head: CHROMATIN REMODELING
CHROMATIN REMODELING
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1CHROMATIN REMODELING
Chromatin is a DNA and protein complex that forms chromosomes within the eukaryotic cell
nucleus. Nuclear DNA does not present in separate longitudinal strands; to suit within the nucleus, it
is strongly compact and bundled around nuclear protein. Chromatins are found in two forms. One
form is less condensed and can be transcribed, called euchromatin. The second type, called
heterochromatin, is highly condensed and is not transcribed usually. Specific molecules called
chromatin remodelers to have the framework for altering chromatin and allowing transcription signals
to enter their DNA strand destinations. Chromatin remodeling is an essential process for controlling
the function of the eukaryotic genome, unwrapping the chromatin to process the gene expression.
Strong DNA binding around histones blocks its exposure to different chromosomal regulatory
proteins, contributing genes silencing.1
Different organisms have a different mechanisms for chromatin remodeling. For starters,
Drosophila midgut regeneration involves Brahma (Brm), the ATPase of the SWItch / Sucrose Non-
Fermentable (SWI / SNF) chromatin remodeling complexes. Brg1, a Brm mammalian homolog, is
crucial for regulating bulge stem cells during regeneration of the skin of the mouse. The deletion of
the SWI / SNF portion increases tissue repair in the liver and ear of the mouse, without inducing
tumor development. In Saccharomyces cerevisiae, the RSC complex first reported as a remodeler. The
RSC complex's ATPase function is triggered by nucleosomal DNA, single-stranded, and/or double-
stranded DNA. However, only one of these DNA-types activates any of the other chromatin
remodeling complexes.2
The structure and function of the different remodeling complexes differ with each other as per
their presence in different organisms. RSC comprises of 17 subunits, and at least three of such
subunits are conserved between RSC and SWI / SNF. Previously, RSC and SWI / SNF are assumed to
be homologous, RSC is considerably more widespread than the SWI / SNF system and is necessary
for the mitotic cell division. RSC and SWI / SNF consist of quite specific elements, such as the in
RSC, Sth1 elements, and the SWI2/Snf2p components in SWI / SNF. All of these are ATPases
composed of Arp7 and Arp9, which are actin-like proteins. The Sth1 subunits areRsc6p, Rsc8p, and
Sfh1p, which are paralogous to the three SWI / SNF subunits, accordingly Swp73p, Swi3p, and
Snf5p.3
RSC places a nucleosome firmly, naturally partly unwound, in a configuration that promotes
attachment of Gal4 to its sites. The complex consists of a membrane adequate to implement classic
characteristics of the architecture of the chromatin. The deletion of RSC makes the creation of usual
nucleosomes more precisely across the UASg, and these nucleosomes interact with binding Gal4 to its
locations. DNA binding proteins in the gene GAL1/10, are the primary determinants of chromatin
architecture.3
Chromatin remodeling is associated with several diseases showing its importance. In
Parkinson’s diseases, altered methylation of DNA in the promoter of the SNCA gene with decreased
methylation in intron 1 that may contribute to the formation of aggregates. In the substantia nigra of
PD patients, methylation is usually reduced, resulting in an altered chromatin environment. Further
data suggest that the expression ofDNMT1 in PD patient brains and transgenic α-synuclein mice is
decreased, withDNMT1 assumed to be sequestered by α-synuclein in the cytoplasm, resulting in
hypo-methylated CpGs.4

2CHROMATIN REMODELING
References:
(1) McLennan, A. Molecular biology; Garland Science: New York, 2013.
(2) Trost, T.; Haines, J.; Dillon, A.; Mersman, B.; Robbins, M.; Thomas, P.; Hubert, A.
Characterizing The Role Of SWI/SNF-Related Chromatin Remodeling Complexes In Planarian
Regeneration And Stem Cell Function. Stem Cell Research 2018, 32, 91-103.
(3) Längst, G.; Manelyte, L. Chromatin Remodelers: From Function To
Dysfunction. Genes 2015, 6 (2), 299-324.
(4) Feng, Y.; Jankovic, J.; Wu, Y. Epigenetic mechanisms in Parkinson's disease. (accessed Mar 20,
2020).