- Review the levels of control of gene expression that include: 1. Chromatin str
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Question
- Review the levels of control of gene expression that include:
1. Chromatin structure and role of chemical modifications of DNA and histones, as
the first “on” switch for turning on eukaryotic gene expression. Define the term
epigenetics.
2. Structural components of eukaryotic genes: coding and proximal and distal
regulatory sequences (enhancers and silencers), and their function. Role and
binding sites of transcription factors and activator and repressor proteins.
3. Transcriptional and post transcriptional levels
4. Pre and post translational control levels
Explanation / Answer
1. The chromatin structure is also defined as the combination of DNA and histone proteins. The histone proteins package the DNA molecules in the nucleus. The nucleosome is called the basic unit of the chromatin structure. The chromatin structure in a way protects the DNA molecules from breakage and enables to fit the double helix DNA in a compact way in the cell. The chromatin structure also helps in the regulation of mitosis and meiosis processes, DNA replication as well as gene expression.
Chemical modifications play a huge role in the gene expression. The N-terminus in the histone molecule protrudes outward from the nucleosome structure and by modifying these N-terminus ends by different enzymes, various chemical groups can be added or deleted. The addition or deletion of such groups directly influences the eukaryotic gene expression.
For example, in the acetylation process, the acetyl (-COCH3) groups are added to the N-terminus end, especially to the positively charged lysines in the histone tails. By such, the positive ends of the histone tails are neutralized and their further binding to the neighboring nucleosome molecules are aborted. The histone deacetylation process is the removal of the acetyl groups from the end tails. In the DNA methylation process, the addition of methyl groups convert the cytosine bases to 5-methylcytosine, which in turn, inhibits the transcription process. ADP ribosylation, ubiquitylation, sumoylation, histone clipping are other process regulating gene expression.
Epigenetics can be defined as the process through which the gene expression can be modified rather than altering the genetic code. It is actually the control activity of gene expression in the development of an organism which does not involve DNA strands.
2.Enhancer: The enhancers are short strands of DNA which are approximately 50-1500 bp long. These short regions of DNA bind to the transcription regulating factors such as activator proteins and enhances the transcription of DNA into RNA and such helps in the regulation of gene expression and also further into the translation of specific proteins. The enhancer regions can be located upstream or downstream as well from the transcription start site and up to almost 1Mbp distance away and they also show cis-acting behavior.
Silencer: The silencers are DNA strands which bind to the transcription regulating factors such as repressor proteins. By binding such they block the RNA polymerase from transcribing DNA into DNA and further blocks the gene expression by repressing the translation of specific proteins. The silencers are found primarily in the upstream regions, almost 20 to 2000 bp away from the start site. They can also be found downstream sometimes or in the 3 prime untranslated regions.
Transcription factors: These are the proteins which take part in the regulation of transcription. By binding to different regulatory sequences, such as enhancer or silencer, these proteins either enhance or inhibit the transcription and in turn the translation process.
Activator: The activators are the regulatory proteins which regulate the gene expression by binding to the regulatory sites such as enhancer sequences nearby to the promoter regions and such activates the gene transcription. The RNA polymerase is activated by the switch on activity and transcription occurs.
Repressor: Repressors are regulatory proteins which bind to the silencer regions and blocks DNA transcription.
3. The eukaryotic gene expression is majorly controlled at the transcriptional level. The processes such as methylations, acetylation, phosphorylations, ubiquitination etc. highly control the eukaryotic gene expression system. By addition or deletion of methyl groups, acetyl groups etc. from the N terminal sites of the histone molecules, the transcription processes are influenced.
The post-transcriptional level gene control includes the control of expression between mRNA and translation and involves-
a) Capping: Turns the 5 prime end of the mRNA to 3 prime end and helps the mRNA from 5 prime exonucleases.
b) Splicing: Removes the non-coding regions or introns from the mRNA to form functional mRNA.
c) Addition of poly A tail: Polyadenylation is the process by which Adenines are added to the 3 prime end of the mRNA. This also helps in the translation process.
d) RNA editing: It helps in the RNA sequence variation.
e) mRNA stability: To increase the half-life of mRNAs.
4. The pre translational control levels are:
a) Capping,
b) Splicing,
c) RNA editing etc.
The post-translational control levels occur in the C or N terminus of the proteins and include the following processes:
a) Phosphorylation: It is the most common post tranlational modification. It mainly occurs on the serine, threonine and tyrosine side chains by the phosphoester bond formation. Through phosphoramidate bond, it occurs on the histidine, lysine and arginine residues and through anhydride linkages on the aspartic and glutamic acid residues.
b) Proteolysis: It is the breakdown of the proteins into smaller polypeptides or amino acids. The proteases enzymes, low pH and high temperature affect the proteolysis process.
c) Carbonylation: Forms the aggregates of proteins.
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