Regulation of Genes in Eukaryotes

The human genome encodes over 20,000 genes; every of the 23 pairs of human chromosomes encodes lots of genes. The DNA withinside the nucleus is exactly wound, folded, and compacted into chromosomes in order to match into the nucleus. It is likewise prepared in order that precise segments may be accessed as wanted via way of means of a particular type.

The first stage of organization, or packing, is the winding of DNA strands round histone proteins. Histones package deal and order DNA into structural gadgets referred to as nucleosome complexes, that could manage the entry of proteins to the DNA regions (Figure 1a). Under the electron microscope, this winding of DNA around histone proteins to shape nucleosomes seems like small beads on a string (Figure 1b). These beads (histone proteins) can flow alongside the string (DNA) and alternate the shape of the molecule

DNA is folded around histone proteins to form (a) a nucleosome complex. These nuclei control the protein’s access to the underlying DNA. Seen under an electron microscope (b), the nuclei look like particles on a string. (credit “micrograph”: artwork modification  by Chris Woodcock)

When the DNA encoding a particular gene is transcribed into RNA, the nucleosomes surrounding that region of the DNA  slide down the DNA to open that particular chromosomal region, and the transcriptional mechanism (RNA polymerase) initiates transcription. Let’s do it (Fig. 2). Nucleosomes can move to open chromosomal structures and expose segments of DNA, but they do so in a highly controlled manner.

The methylation of DNA and histones clogs nucleosomes. Transcription factors are unable to bind to DNA, and genes do not function.

1.  Acetylation of histones causes nucleosome packing to relax. Transcription factors can bind to DNA and cause genes to be expressed.

Figure 2. Nucleosomes can slide along the DNA. When nucleosomes are in close proximity (above), transcription factors cannot bind and gene expression is turned off. If the nucleosomes are far apart (bottom), the DNA will be exposed. Transcription factors bind to allow gene expression. Histone and DNA modifications affect nucleosome spacing.

The movement of histone proteins is dependent on signals found on both histone proteins and  DNA. These signals are tags added to histone proteins and DNA to tell histones whether a chromosomal region should be opened or closed (Figure 3 illustrates changes to histone proteins and DNA). These tags are not permanent but can be added or removed as needed. These are chemical modifications (phosphate, methyl, or acetyl groups)  attached to specific amino acids in proteins or to nucleotides in DNA. The tags don’t change the base sequence of the DNA, but they do change how tight the DNA is around the histone proteins. DNA is a negatively charged molecule; therefore, a change in histone charge will alter the degree of tightness of the  DNA molecule. When unmodified,  histone proteins have a large positive charge; by adding chemical modifications such as acetyl groups, the charge becomes less positive.

You can also change the DNA molecule itself. This happens in a very specific area called the CpG island. These are frequent stretches of cytosine and guanine dinucleotide (CG) DNA pairs found in the promoter region of a gene. If this configuration is present, the cytosine member of the pair can be methylated (a methyl group is added). This change changes the way DNA interacts with proteins. This includes histone proteins that control access to that area. The highly methylated (hypermethylated) regions of DNA  with deacetylated histones are tightly coiled and transcriptionally inactive.

Histone proteins and DNA nucleotides can both be chemically changed. Nucleosome spacing and gene expression are affected by changes. (updated work from the National Institutes of Health)

Epigenetic means “around the genetic”. Changes that occur on Histone and DNA proteins do not modify nucleotide sequences and are not permanent. Instead, these changes are temporary (although they usually exist through some cell division rings) and modify the chromosome structure (open or close) when needed. A gene can be enabled or disabled depending on the location and modified protein and DNA Histone. If a gene should be negative, protein histone and DNA are amended around this gene encoding chromosome area. This opens up the chromosomal region to allow  RNA polymerase and other proteins, called transcription factors, to access to bind to the promoter region, located just above the gene, and initiate transcription. If a gene remains inactivated or silenced,  histone proteins and DNA will exhibit different changes signaling a closed chromosome profile. In this closed configuration,  RNA polymerase and transcription factors do not have access to the DNA and transcription cannot occur.

Transcription of a gene in eukaryotes requires the action of  RNA polymerase to bind to the sequence upstream of the gene to initiate transcription. However, unlike eukaryotic cells,  eukaryotic RNA polymerases require other proteins or transcription factors to promote transcription initiation. Transcription factors are proteins that regulate the transcription of target genes by binding to promoter sequences and other regulatory sequences. The RNA polymerase itself cannot initiate transcription in the eukaryotic cells. Transcription factors must first bind to the promoter region and recruit RNA polymerase to the site where transcription is established.

Regulation of Gene Expression in Eukaryotes

We are saying that a gene is “expressed”. If the gene encodes a protein, one may fairly advocate that the “expression” of a gene is how a whole lot of practical protein is made. But what if the gene does now no longer encode a protein, however alternatively a few practical RNA. Then, in this case, “expressed may suggest how a whole lot of the practical RNA is made. In case any other man or woman may fairly propose that “expression” simply refers back to the preliminary step in developing a replica of the genomic data. By that definition, one may need to depend on what number of full-duration transcripts are being made. Is it the variety of give-up merchandise encoded via means of the genomic data or is it the variety of reads of the data that is critical to describe “expression”? Unfortunately, in exercise, we regularly locate that the definition relies upon the context of the discussion. Keep that in mind. For the sake of ensuring that we’re speaking about approximately the identical factor, in Bis2A we’ll try to use the term “expression” ordinarily to explain the advent of the very last practical product(s). Depending on the unique case, the very last product can be a protein or RNA species.

How are Genes Regulated in Eukaryotes?

The gene expression in the eukaryotic cells is controlled by both repressors and transcriptional activators. Eukaryotic repressors, like their prokaryotic counterparts, bind to specific DNA sequences and suppress transcription. Eukaryotic repressors interfere with the binding of certain transcription elements to DNA in a few circumstances. The binding of a repressor near the transcription start sites online can, for example, inhibit the interaction of RNA polymerase or modern transcription elements with the promoter, similar to how repressors move in the bacteria. Other repressors compete with activators for regulatory sequence binding. Because the activator lacks its activation area, some of these repressors include an equivalent DNA-binding area. As a result, they are bound to each other.

Conclusion

Gene expression regulation, or gene regulation, encompasses a  range of mechanisms used by the cells to increase or decrease the making of specific gene products (proteins or RNA). Complex gene expression programs are widely observed in biology, such as activating developmental pathways, responding to environmental stimuli, or adapting to fresh food sources. Virtually any step in gene expression can be regulated, from transcription initiation to RNA processing and post-translational modification of proteins. Often one gene regulator controls another gene regulator, and so on, in a gene regulatory network.