The Role of Chromatin in Transcriptional Control of Gene Expression

Introduction

Chromatin is a mass of genetic material made out of deoxyribonucleic acid (DNA) and proteins that gather to shape chromosomes in eukaryotic cell division and is found in the center of a cell (Kouzarides, 2007, 693). The role of chromatin entails packing of DNA into less large units that fit in the nucleus. They also contain protein structures called histones, and DNA. DNA is wrapped around the base of histones, and it is converted to nucleosomes which are in turn collapsed to form chromatin fiber (Rice, & Allis, 2001, 263). The structure of chromatin defines its physical organization of chromatin inside the eukaryotic nucleus and how arrangement impacts chromatin procedures like transcription (Kelly, Wickstead & Gull, 2005, 1435). The reiterating element of chromatin, the nucleosome, comprises about 147 base pairs of DNA covered around eight histone protein cores. Linker DNA, a loft of 80 base pairs long, attaches two histones between every nucleosome core element (Taube & Craig, 2006, 10). Euchromatin contributes in the active transcription of DNA to mRNA products, and the RNA polymerases are fixed to DNA hence inducing transcription procedure in gene expression.

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Chromatin is a packed DNA within the cell and nucleosome is its fundamental unit. Chromatin is comprised of four core histones, which are H2A, H2B, H3, and H4 and it is wrapped with 147 base pairs of DNA (Taube & Craig, 2006, 3). The core histones are globular in shape except for their N-terminus tails that are unstructured (Kouzarides, 2007, 693). There are at least eight different types of modification found on histones, but the major one is; acetylation, methylation, and phosphorylation; other modifications ubiquitination, APD ribosylation, sumoylation, deimination, and proline isomerization. Acetylation, phosphorylation, methylation, and ubiquitination have been associated with activation while ubiquitination, deimination, sumoylation, and proline isomerization have been associated with repression (Kouzarides, 2007, 693).

Acetylation

Histones are positive charges that neutralize DNA which is negatively charged from phosphate groups (Rice, & Allis, 2001, 263). This activity occurs when acetylation opens up the DNA from wrapping on histones where the positive charge is neutralized allowing RNAP to bind to the DNA and start transcription. The terminal end of histones has positive lysine groups that tightly bond with DNA that can acetylate or deacetylates histones (Rice, & Allis, 2001, 264). Deacetylation process removes acetyl groups on lysine allowing DNA to resume heterochromatin form. In this process, RNAP gets room to get in and transcribe the DNA. This occurrence is a modification that is associated with transcription activation. Acetyltransferases are divided into MYST, GNAT and CBP/p300 enzymes which are involved in the change of more than one lysine but have some limited specificity (Rice, & Allis, 2001, 264). Deacetylation refers to the reversal of acetylation, and it correlates with transcription repression. Apart from regulating transcription, acetylation serves to control replication, condensation, and repair of the DNA. Acetylation is recognized by bromodomains, and histone acetylating adds acetyl to an end of a histone protein where reversible acetylating of internal lysine in histone amino-terminal has a long domain linked positively to transitional activation. The histone protein is usually abundant and plays a crucial role in condensation and relaxation processes of the DNA (Rice, & Allis, 2001, 264).

Gene Expression

Gene expression is a vital biological process that takes place in our bodies countless times per day. Throughout every day the human body is continuously making thousands of proteins through the process called gene expression (Teixeira, 1998, 1504). Gene expression is the process by which our bodies use our genetic material called genes to create new proteins. It is essential because the body is in constant need of a fresh supply of cells to grow or repair our bodies. There are two basic steps to gene expression which are transcription which is the process of DNA being copied onto a template for translation, the second step, the process of the body taking the mRNA template and making it into polypeptides (Teixeira, 1998, 1504). Each of these processes is a complicated process which is why it is so amazing that it happens so fast and in such vast quantities every day.

It is essential to focus on the gene and how it works before understanding gene expression. A gene is the basic physical and functional unit of heredity (Taube & Craig, 2006, 3). Each gene is a specific spot on a chromosome, and each chromosome can have thousands of genes because of the way sexual reproduction works humans have two of every gene one from the father and one from the mother. In each of these genes, one is dominant, and the other is recessive depending on the way they are paired in different phenotypes which is the physical traits expressed from the genotypes. Genes themselves are made up of strands of DNA and can be made from hundreds to millions of DNA bases depending on the gene (Fraser & Bickmore, 2007, 414). Genes are responsible for the creation of proteins which determine cell functions which is gene expression.

Gene expression happens in two steps the first of which is called transcription. According to Uzureau et al. (2008, 1121), "Transcription is the process of copying out the DNA sequence of a gene in a similar alphabet of RNA." The purpose is to take the DNA from our genes and make a mRNA copy of it. The RNA copy that is made from transcription is called the transcript. RNA polymerase is an enzyme that plays a central role in the transcription of DNA (Kelly, Wickstead & Gull, 2005, 1435). RNA polymerase is a very large enzyme, and there are three different types each serving a different purpose. "RNA polymerase I transcribe rRNA genes, RNA polymerase II transcribes mRNA, miRNA, snRNA, and snoRNA genes, and RNA polymerase III transcribes tRNA and 5S rRNA genes"(Uzureau et al., 2008, 1121). Essentially the RNA polymerase in transcription takes a single strand of DNA and using it as a template to make the new strand of mRNA.

The role of chromatin in transcriptional control of gene expression is manifested in the three stages to DNA transcription which is initiation, elongation, and termination (Hernandez & Cevallos, 2014, 2416). In the first stage, initiation takes place to split the DNA into single strands so that the DNA polymerase can transcribe it. It happens when the RNA polymerase binds to a DNA polymerase sequence called a promoter which splits the DNA strand into two single strands of DNA. The second step in the transcription of DNA is called elongation, and the purpose of this stage is to use the single strands created in the initiation and use one to build the mRNA. Elongation starts after the DNA polymerase splits the DNA into two separate strands then the RNA polymerase uses one of the strands which is then called the template strand. The RNA polymerase then takes the template strand and builds and mRNA strand using the complimenting nucleotides (Hernandez & Cevallos, 2014, 2418). The complementing nucleotides are the nucleotides that fit within the DNA strand together so for each purine base the RNA polymerase will change it to the complimenting purine base and likewise for each pyrimidine base. Another change that the RNA polymerase makes while transcribing the DNA is instead of using Thymine it uses Uracil (Hernandez & Cevallos, 2014, 2418). It is because using Uracil requires less energy but Thymine is easier to repair in DNA if it is damaged. For example, if the strand of DNA given to the RNA polymerase to transcribe is AGTC, then the RNA polymerase will transcribe it onto the new mRNA as UCAG transcribing the compliments of each nucleotide and replacing each Thymine with Uracil (Hernandez & Cevallos, 2014, 2419). The RNA polymerase makes these changes when transcribing DNA which prepares the mRNA stand to be ready for translation. Even though the mRNA is ready for translation, there is still one step left in the process of transcription. Termination is the last step, and the purpose of this step is to get the RNA polymerase to release from the mRNA strand so it can be used in translation. For the RNA polymerase to split off from the DNA strand, the DNA uses terminators to signal the RNA polymerase that the transcription is complete and it is time to release it. The terminators are a sequence of the DNA which is designed to end transcription (Hernandez & Cevallos, 2014, 2419).

After transcription ends the cell now has a mRNA strand that is ready for the second major step of gene expression which is the translation. Translation is the process of taking the strand of mRNA and turning it into polypeptides or proteins (Kelly, Wickstead & Gull, 2005, 1435). These proteins are made from groups of three nucleotides called codons. Overall there are 61 different codons that the nucleotides can make. There are a few specific codons one called the start codon, and it is when the AUG nucleotides are together. The start codon is what tells the ribosome to start creating the protein. The other type of specialty codon is the stop codons, and there are several of them that alert the ribosome when the formation of the protein is complete. There is an enzyme that is necessary for the translation step in gene expression called tRNA. The tRNA binds to the mRNA codons to the amino acids that they are encoding using an anticodon. Ribosomes are where all proteins are made, and each ribosome closes around the mRNA that it is translating to create the new protein.

Much like chromatin transcription, the process for translation involves three steps (Kruger et al., 2015, 153). The first step initiation happens when the ribosome encloses around the mRNA for protein production to begin. Step two is elongation which is where the amino acid chain elongates and the mRNA is read. For every new codon the tRNA binds, it is studied so that the ribosome can create the amino acids. The last step in translation is termination which happens when the tRNA reaches the stop codon (Dahse, & Kosmehl, 2004, 154). After the tRNA reaches the stop codons, there are release factors which cause the last codon to be produced with water which disconnects the tRNA and releases the newly created protein (Kruger et al., 2015, 153).

Conclusion

Euchromatin contributes in the active transcription of DNA to mRNA products, and the RNA polymerases are fixed to DNA hence inducing transcription procedure in gene expression. The hereditary material in chromatin is made of DNA and proteins that gather to shape chromosomes in eukaryotic cell division and is found in the center of a cell Chromatin plays an integral role in the transcriptional control of gene expression which is one of the most important biological processes in all of life. Even the smallest organisms like bacteria rely on this process to grow and heal. Chromatin controls gene expression through alteration of its contents, and it contains essential materials with determines the physical appearance - the modification of DNA results to a different gene formation hence different physical characteristics.

References

Dahse, R. & Kosmehl, H., 2004. Cell separation and gene expression analysis in a tumor-stroma interaction model. Image Analysis & Stereology, 23, pp. 153-157.

Fraser, P. & Bickmore, W., 2007. Nuclear organization of the genome and the potential for generegulation. Nature, 447, pp. 413-417.

Hernandez, R. & Cevallos, A....