Professional Documents
Culture Documents
In eukaryotes, DNA is tightly wound into a complex called chromatin. Thanks to the process of chromatin
remodeling, this complex can be "opened" so that specific genes are expressed.
Aa Aa Aa
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. In recent years, researchers have discovered a great deal about chromatin Chromatin
remodeling, including the roles that different protein complexes, histone variants, and biochemical modifications play in this process. However, a
great deal remains to be learned before chromatin remodeling is fully understood.
https://www.nature.com/scitable/topicpage/chromatin-remodeling-in-eukaryotes-1082/ 1/6
09/01/2020 Chromatin Remodeling in Eukaryotes | Learn Science at Scitable
A nucleosome core particle consists of eight histone proteins (two each of H2A, H2B, H3 and H4) and 146 base pairs of double-stranded DNA. The composition of nucleosomes
is not set in stone, however. Indeed, canonical histones can themselves be replaced by histone variants or modified by specific enzymes, thereby making the surrounding DNA
more or less accessible to the transcriptional machinery.
So far, a number of histone variants have been found and localized to specific areas of chromatin. For instance, H2A.Z is a variant of H2A and is often enriched near relatively
inactive gene promoters. Interestingly, H2A.Z does not take its place during replication when the chromatin structure is established. Instead, the chromatin remodeling complex
SWR1 catalyzes an ATP-dependent exchange of H2A in the nucleosome for H2A.Z (Wu et al., 2005).
CENP-A is another known histone variant that has been found to be associated with centromeres. Originally localized to the centromere through immunofluorescence studies,
CENP-A was believed to be involved in centromeric activity during cell division. But, once the CENP-A protein was isolated and sequenced, it was shown to have sequence
homology to H3, suggesting that CENP-A actually replaces canonical H3 near the centromere. Some experiments suggest that these variant histones that occur in particular
areas of the genome may assist in the specific regulation of chromatin behavior and gene transcription from these areas (Li et al., 2005).
https://www.nature.com/scitable/topicpage/chromatin-remodeling-in-eukaryotes-1082/ 2/6
09/01/2020 Chromatin Remodeling in Eukaryotes | Learn Science at Scitable
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 (Turner, 2005). While the most common additions are acetylation and
methylation of lysine residues, many more types of modifications have also been observed, including phosphorylation, 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.
https://www.nature.com/scitable/topicpage/chromatin-remodeling-in-eukaryotes-1082/ 3/6
09/01/2020 Chromatin Remodeling in Eukaryotes | Learn Science at Scitable
machines, called the SWI/SNF and SAGA histone acetylase complex, is recruited to the yeast HO gene promoter by the SWI5 activator. Activator-dependent chromatin
modification then moves the nucleosome out of the way so that RNA polymerase II can reach the promoter regions of the DNA (Struhl, 1999).
Chromatin remodeling activity by SWI/SNF or other remodeling machines can also be required for recruiting additional chromatin remodeling activity to the site, as well as
additional downstream sites. Modifications at a promoter can occur in multiple steps that are independently regulated, and additional modifications can occur stepwise
stretching from the point of the first modification along the DNA strand in a downstream direction toward the promoter. These modifications open up an elongated region of
active chromatin and allow for a wide range of intermediate, transcriptionally inactive states for the eukaryotic promoter. Promoters can also be poised with RNA polymerase
bound but not elongating the mRNA; in yeast, up to 15% of sites have such stalled transcription. Changes in gene expression during the specific developmental stages of an
organism or cell coincide with fluctuations in the levels of each of the specific protein complexes involved in chromatin remodeling (Struhl, 1999).
DNA Methylation
Another means by which transcription is controlled is through methylation of the DNA strand itself. Not to be confused with histone methylation, methylation of the DNA strand
involves cytosine bases of eukaryotic DNA being converted to 5-methylcytosine, resulting in the repression of transcription, particularly in vertebrates and plants. The altered
cytosine residues are usually immediately adjacent to a guanine nucleotide, resulting in two methylated cytosine residues set diagonally to one another on opposing DNA
strands (Figure 3).
Figure Detail
Heavily methylated regions of DNA with elevated concentrations of these so-called CpG groups are often found near transcription start sites. In an interestingly coordinated
process, proteins that bind to methylated DNA also form complexes with proteins involved in deacetylation of histones. Therefore, when the DNA is in a methylated state,
nearby histones are deacetylated, resulting in compact, semipermanently silent chromatin. Likewise, demethylated DNA does not draw deacetylating enzymes to the histones,
but it often attracts histone acetyltransferases, allowing histones to remain acetylated and promoting transcription.
Summary
Storage of eukaryotic DNA in small, compact nuclei requires that this DNA be tightly coiled and compacted in the form of chromatin. However, the structure of chromatin also
appears to serve a second, possibly more important role, in that it gives eukaryotic cells the capability to exert complex levels of control over gene expression.
As described throughout this article, chromatin and the DNA sequences it contains are constantly undergoing modifications, thereby periodically exposing different regions of
DNA to transcription factors and RNA polymerases. The cumulative effects of these changes are various states of transcriptional control and the ability of eukaryotic cells to turn
genes on and off as needed. This complexity provides eukaryotes with a means of making the most of a relatively small number of genes. However, much research remains to
https://www.nature.com/scitable/topicpage/chromatin-remodeling-in-eukaryotes-1082/ 4/6
09/01/2020 Chromatin Remodeling in Eukaryotes | Learn Science at Scitable
be performed before investigators precisely understand how the many mechanisms of chromatin remodeling operate, as well as how they work together to result in the complex
patterns of gene expression characteristic of eukaryotic cells.
https://www.nature.com/scitable/topicpage/chromatin-remodeling-in-eukaryotes-1082/ 6/6