Comprehensive Review on Eukaryotic Chromatin Remodeling Processes

This report provides a comprehensive review of eukaryotic chromatin remodeling, a crucial process for regulating gene expression. It begins by defining chromatin and its role in cell division, DNA transcription, and repair. The report then delves into the process of chromatin remodeling, explaining how it allows DNA binding proteins and transcription factors to control gene expression. The core of the review explores two main types of chromatin remodeling: those involving protein complexes that modify histone proteins, and those involving ATP-dependent molecular motors. Four ATP-dependent remodeling complexes (Mi-2, ISWI, SWI/SNF, and Ino8o) are discussed, including their subunits and functions. The report also highlights the role of the INO80 complex in spermatogenesis and DNA repair. Furthermore, the report discusses the impact of abnormal chromatin deregulation on cell function, leading to neurodevelopmental disorders, immunodeficiency diseases, and cancer. Specific conditions, such as ATRX syndrome and CHARGE syndrome, are examined in the context of chromatin remodeling complexes, and the report concludes by emphasizing the importance of understanding chromatin remodeling for comprehending cellular processes and disease mechanisms.

Running head: REVIEW ON CHROMATIN REMODELING
REVIEW ON CHROMATIN REMODELING
Name of the Student
Name of the University
Author Note

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REVIEW ON EUKARYOTIC CHROMATIN REMODELLING
Answer 1
Chromatin is a form of genetic material that is composed of DNA, RNA, and protein. It is
a complex mainly of DNA and histone that is commonly observed in eukaryotic cells (1). These
genetic substances condense and help to form chromosomes at the time of cell division.
Chromatin is generally located in the nucleus of a cell. Chromatin shows an essential role in
different biological procedures to take place, such as DNA transcription, replication, and cell
division, genetic recombination, and also in DNA repair.
Chromatin remodeling is the process of chromatin reorganization from a condensed form
to a genetically effective way permitting different DNA binding proteins and transcription
factors to regulate gene expression. Several studies have shown that if the chromatin remains in
this condensed state, it is quite challenging to access the DNA. Therefore, specifically in
eukaryotic cells, some genes cannot be expressed since RNA polymerase, and the proteins
known as transcription factors are not able to regulate the DNA. Hence, the chromatins must
open to express the gene, and this opening procedure is known as chromatin remodeling that
plays a significant role in proper cell functioning (2).
Answer 2
Types of chromatin remodeling complexes: There are two different types of chromatin
remodeling: the first category involves protein complexes that alter the chromatin structure by
transforming the histone protein. The second category includes molecular motors that are ATP-
dependent remodeling factors. Four ATP-dependent remodeling complexes are present in
eukaryotic cells. They are Mi-2, ISWI, SWI/SNF, and Ino8o.

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REVIEW ON EUKARYOTIC CHROMATIN REMODELLING
SWI/SNF is the complex that is first discovered in Saccharomyces cerevisiae (yeast). It consists
of four subunits that are homolog of SWI2/SNF2 yeast proteins, SNF5, SWP73, and SWI3.
SWI/SNF category is further distributed into two subparts that contain Drosophila BAP (Brm
associated proteins), yeast SWI/SNF, and mammalian BAF compound, when the other part
consists Drosophila PBAP, yeast RSC, mammalian PBAF (3). In the ISWI group, the
remodeling complexes are dCHRAC and dNURF, is first discovered in the embryo of
Drosophila. Later, these groups are identified in mice, humans, yeast, and Xenopus. CHD or Mi2
group remodeling complexes are found in human, Xenopus laevis, Drosophila Polycomb. An
Mi-2 homolog is also observed in Drosophila, known as dMi-2. The INO8o complex comprises
subunits like Rvb1, Arp5, Rvb2, Arp8, Ies6 and Ies2. This complex is highly preserved in
humans. It is also identified in mice.
Answer 3
The remodeling complex INO8O, which is found in mouse, acts as an essential meiotic
factor and plays a vital role in spermatogenesis. The researcher performed an experiment where
they first knocked out Ino80 (4). They have shown that this remodeling complex is involved in
DNA repair. They observed that INO80 is expressed at the time of spermatocytes during the
meiotic prophase I. studies have reported that the SWI/SNF complex identified in yeast consists
of 11polypepetides, which has over 1.5MDa molecular weight. This complex comprises of
ATPase Swi/Snf2, two actin-related proteins, and other subunits. This remodeler performs
adenosine triphosphate hydrolysis to modify the histone-DNA interactions that resulted in
histone octamer sliding along with the DNA or complete removal of that octamer from the DNA.
The ISWI complexes facilitate DNA repair by activation of pol III transcription and help in the
differentiation of somatic cells (5). This complex also assists in nucleosome sliding.

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REVIEW ON EUKARYOTIC CHROMATIN REMODELLING
Answer 4
The chromatin alteration complex plays an essential role in gene expression and aid in
maintaining and development of cell function. Abnormal chromatin deregulation may often
occur, which leads to faults in genetic expression, and these flaws are caused by acquired or
inherited mutation of genes and their enzymes. This deregulation often causes to occur different
neurodevelopmental disorders, immunodeficiency disease also cancer. Several conditions are
associated with chromatin remodeling complex. They are ATRX syndrome that is α-thalassemia
myelodysplasia syndrome and α thalassemia X-linked mental retardation (6). The mutation in
ATRX that is an SNF-2 related ATPase is responsible for causing this disease. Another disease is
CHARGE syndrome, which is an autosomal disorder that is related to the haploinsufficiency of
CHD7. This gene expresses CHD family ATPase CHD7. Neurodevelopmental disorders are
associated with the chromatin-remodeling complex SWI/SNF. The disease includes mental
retardation, coffin-siris syndrome, and the responsible protein is BAF250A.

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REVIEW ON EUKARYOTIC CHROMATIN REMODELLING
References
1. Zhang P, Torres K, Liu X, Liu CG, E Pollock R. An overview of chromatin-regulating
proteins in cells. Current Protein and Peptide Science. 2016 Aug 1;17(5):401-10.
2. Mandemaker IK, Vermeulen W, Marteijn JA. Gearing up chromatin: A role for chromatin
remodeling during the transcriptional restart upon DNA damage. Nucleus. 2014 May 1;5(3):203-
10.
3. Kadoch C, Crabtree GR. Mammalian SWI/SNF chromatin remodeling complexes and cancer:
Mechanistic insights gained from human genomics. Science advances. 2015 Jun
1;1(5):e1500447.
4. Serber DW, Runge JS, Menon DU, Magnuson T. The mouse INO80 chromatin-remodeling
complex is an essential meiotic factor for spermatogenesis. Biology of reproduction. 2016 Jan
1;94(1):8-1.
5. Aydin ÖZ, Vermeulen W, Lans H. ISWI chromatin remodeling complexes in the DNA
damage response. Cell cycle. 2014 Oct 1;131(9):3016-25.
6. Dyer MA, Qadeer ZA, Valle-Garcia D, Bernstein E. ATRX and DAXX: Mechanisms and
Mutations. Cold Spring Harbor perspectives in medicine. 2017 Mar 1;7(3):a026567.