Genetics Lecture 8 - Regulation of Gene Expression PDF

Genetics Regulation of gene expression LECTURE (8) Regulation of gene expression DR. El-Sawy 0  Genetics...

Genetics Regulation of gene expression LECTURE (8) Regulation of gene expression DR. El-Sawy 0  Genetics Regulation of gene expression Central Dogma of molecular biology: Definition: Mechanisms used to increase or decrease the production of specific gene products (protein or RNA). Levels of eukaryotic gene regulation: 1. Alteration of gene content (control at DNA level). 2. Transcriptional regulation (control at transcription level). 3. Post-transcriptional regulation. DR. El-Sawy 1  Genetics Regulation of gene expression  Increase number of gene copies  increase production of protein  Ex: Malignant cells develop resistance to methotrexate by increasing number of genes for di-hydrofolate reductase which is the target for methotrexate. Gene Amplification  Removal of a gene or genes from the genome.  Example: Complete loss of all genes in red blood cells during development (These discard their nuclei once sufficient hemoglobin RNA is synthesized). Gene diminution DR. El-Sawy 2  Genetics Regulation of gene expression  Plays a major role in the generation of antibodies (immunoglobulins) produced by B-Cells. Gene Rearrangement (recombination) Clinical application  Methotrexate is an anticancer drug which inhibits di-hydrofolate reductase  With long term therapy, cancer cells develop resistance to this drug by increasing the number of genes for di-hydrofolate reductase by gene amplification DR. El-Sawy 3  Genetics Regulation of gene expression A. Chromatin remodeling:  The methyl group is added to the C5 of cytosine base in GC rich regions (by DNA methylase enzyme).  ↓ rate of transcription as it converts the active euchromatin into inactive heterochromatin.  Reactivation occurs again by demethylation. DNA cytosine methylation  Acetylation of lysine residues of histone proteins  Removal of the positive charges ↓affinity between histone and DNA.  This makes RNA polymerase, and transcription factors easier to bind promoter region leading to activation of transcription  Deacetylation of histone by deacetylase enzyme reverses this Histone acetylation process leading to inactivation of transcription. DR. El-Sawy 4  Genetics Regulation of gene expression B. DNA regulatory regions:  They are specific DNA sequences which are present on the same gene upstream from the transcription start initiation point, they include: Enhancer Silencer (Repressers)  Increase rate of gene expression  Decrease rate of gene expression DR. El-Sawy 5  Genetics Regulation of gene expression  Alternative RNA processing leading to production of different peptides with different functions. Alternative splicing  m.RNA half-life is variable  ranging from a few minutes to days.  The longer the poly A tail the longer the half- life time of mRNA as it stabilizes mRNA by protecting its 3’ end from RNA stability attack by exonuclease enzyme. DR. El-Sawy 6