The Importance Of Chromatin Remodeling In Understanding Gene Expression

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DNA, at its core, is a genetic blueprint that contains all the relevant information needed to support life. Embedded within the DNA sequence are discrete regions known as genes; these sequences are expressed as proteins, which are responsible for all the actions and mechanisms in cells. The genetic code contained within each cell is large, comprising 3 billion bases and spanning over 5 feet in length. In order to fit all of this information into each cell, DNA must be compacted tightly. “Chromatin” is the term used to describe the three-dimensional structures DNA adopts in the cell, that enable this large amount of genetic material to fit in a 10 micron cell space. The base unit of chromatin is the nucleosome, which is composed of DNA wrapped around a histone octamer core. This “beads-on-a-string” structure can be further compacted and folded to generate the condensed chromatin format often visualized in textbooks, i.e. the chromosome.

Chromatin also has fundamental roles in gene expression, as the accessibility, or “openness” of chromatin structure controls access to DNA by transcription factors and other regulatory proteins. Chromatin accessibility is regulated by several mechanisms. First, the histone proteins contained within nucleosomes can be heavily modified, leading to tightening or relaxing of chromatin and thus altered access to the underlying DNA sequence. These modifications are often called “epigenetic” modifications, because they are sequence-independent regulators of the DNA code. Second, the physical localization of nucleosomes can also impact gene expression, because DNA wrapped around nucleosomes is often difficult to contact. Together, the processes of nucleosome modification and reorganization of nucleosomes on DNA is termed Chromatin Remodeling.

Chromatin remodeling processes are critically important to our understanding of how certain genes become expressed or silenced. Indeed, regulation of chromatin structures is essential to proper functioning of a cell, and altered regulation and histone modifications can result in impaired cellular function and development of disease. As a result, epigenetic research may enable discovery of the predisposing factors and causes of diseases. For instance, changes in DNA methylation and / or histone modifications can influence the development of cancer and neurodegenerative diseases; by understanding these changes, it may be possible to identify new therapeutic targets or change the way they are medically addressed.

As discussed above, there are various factors that impact chromatin remodeling. Specific histone modification, such as histone lysine acetylation, promote open chromatin structures and access by transcriptional machinery, thus promoting gene expression. These modifications can also change when exposed to certain modifying enzymes, resulting, for example, in histone lysine 27 methylation, which is associated with gene silencing. Larger chromatin remodeling complexes interact with sets of histone modifications to rearrange nucleosome positions on the DNA template, further influencing chromatin structure and gene expression patterns. Thus, being able to identify the factors affecting chromatin remodeling and histone modifications is one of the most crucial aspects of effective epigenetic research.

EpiCypher offers many of the products required for accurate and precise chromatin remodeling studies, including modified designer nucleosomes (dNucs), which are necessary to study many chromatin interacting proteins and enzymes. At EpiCypher.com, there is a comprehensive catalog of nucleosome substrates, including dNucs, Recombinant Nucleosomes (rNucs), Oncogenic Nucleosomes (OncoNucs), as well as highly specialized EpiDyne Chromatin Remodeling Nucleosome Substrates. EpiCypher also offers Variant Nucleosomes (containing defined histone variants), Methyl DNA Designer Nucleosomes, and Nucleosome Components and Subunits. The researchers at EpiCypher provide rigorously validated and highly pure materials for the execution of epigenetic studies. EpiCypher also offers Recombinant Proteins such as their EpiDyne Chromatin Remodeling Enzymes, Histone Binding Domains, and Modifying Enzymes. In addition, they offer best-in-class SNAP-ChIP Certified Antibodies for ChIP-seq assays, validated against a defined nucleosome substrate, as well as Reagents for their CUTANA CUT&RUN / ChIC assays. Visit EpiCypher.com today to get a full list of their offerings.

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