Explain chromatin remodeling in Eukaryotes: what it is (provide a definition), w

Question

Explain chromatin remodeling in Eukaryotes: what it is (provide a definition), what it does to DNA, and how chromatin changes can be inherited by daughter cells. Underline the following terms in your answer: histone tails, promoter, DNA replication, and acetylation. Make sure that your answer is complete and cohesive, and that relationships between chromatin structure and DNA availability are clearly explained. Include 1 figure. You are required to illustrate how chromatin changes can be transferred from DNA ahead of a replication fork (i.e., not yet replicated DNA) to the DNA behind the fork.

Explanation / Answer

Various molecules called chromatin remodelers provide the mechanism for modifying chromatin and allowing transcription signals to reach their destinations on the DNA strand.

If the DNA strand in a single human cell were stretched out, it would measure several meters in length. Thus, this strand must coil and kink many times over in order to fit into the cell's nucleus, which has a diameter only about one-tenth that of a human hair. To achieve this highly condensed form, the DNA winds itself around proteins called histones, thereby forming a complex known as chromatin. Interestingly, chromatin not only serves as a way to condense DNA within the cellular nucleus, but also as a way to control how that DNA is used. In particular, within eukaryotes, specific genes are not expressed unless they can be accessed by RNA polymerase and proteins known as transcription factors. In its default state, the tight coiling that characterizes chromatin structure limits the access of these substances to eukaryotic DNA. Therefore, a cell's chromatin must "open" in order for gene expression to take place. This process of "opening" is called chromatin remodeling, and it is of vital importance to the proper functioning of all eukaryotic cells.

Histone sequences are highly conserved. Extending from each of the histones is a "tail," called the N-terminal tail because proteins have two ends--an N terminus and C terminus. Here, the C terminus forms a globular domain that is packaged into the nucleosome. The other end of the histone is more flexible and capable of interacting more directly with DNA and the different proteins within the nucleus. Specifically, histone modification involves covalent bonding of various functional groups to the free nitrogens in the R-groups of lysines in the N-terminal tail. Early research has linked differing levels of acetylation and methylation on the histones to altered rates of DNA transcription. While the most common additions are acetylation and methylation of lysine residues, many more types of modifications have also been observed, includingphosphorylation, a common posttranslational modification. The different types of modifications, which have been called the "histone code," are put in place by a variety of different enzymes, many of which have yet to be fully characterized. Thus, the story of the remodeling machinery continues to be told through a variety of experiments, and much remains to be revealed.

Epigenetics is the study of changes in gene expression patterns due to mechanisms other than mutations in the underlying DNA sequence. Epigenetic modifications are inherited by daughter cells during cell division. The changes in gene expression associated with epigenetics are governed by alterations in chromatin structure. While most genes in autosomal cells are simultaneously expressed from both alleles, a small proportion of genes are expressed in a monoallelic fashion. Imprinting is the process through which one of two alleles for a given gene is silenced in a parent-of-origin specific pattern. Imprinting is considered a form of epigenetics because it leads to heritable changes in gene expression despite a lack of changes in the genomic code.

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