1. REGULATION OF GENE Expression-note .pptx

Highlights gene expression pattern in cells
Gene expression and regulation
Mechanism of gene expression In prokaryotic and eukaryotic

1. REGULATION OF GENE EXPRESSION A. A. OSUNTOKI, Ph.D.

2. A nucleoprotein complex Contains the genetic material Polygenic Consists of DNA and basic proteins The protein kind and types may vary in different cell types Twenty three (23) pairs in humans THE CHROMOSOME

3. Contained on the chromosome The unit of heredity Finite sequence of nucleotides In eukaryotes, each cell contains the full genetic complement (exception: mature rbc) Made up of DNA in most life forms Contains information on the blueprint for the organism Sequence of DNA capable of independent expression The major function is to specify the sequence of amino acids in a protein Determines the structure of a protein THE GENE

4. Genetic information is organized into genes or cistrons The message is encoded in a triplet of bases called codons Codons specify the amino acids to be incorporated into a growing protein chain Codons also specify chain termination There are 64 codons 61 codons specify amino acids 3 codons specify chain termination The code is degenerate The code is universal Codons specifying the same amino acids are called synonyms THE GENETIC CODE

5. GENE EXPRESSION A gene is said to be expressed when the gene product is being produced. The flow of genetic information is depicted below: DNA RNA PROTEIN

6. The implication is that DNA makes RNA which in turn makes proteins. This is what is generally referred to as the Central dogma of gene expression. The formation of daughter DNA strands is called replication . The transfer of genetic information to RNA is called transcription . All RNA types are transcribed from DNA. The conversion of the genetic information into a polypeptide is called translation.

7. REGULATION OF GENE EXPRESSION The cellular control of the amount and timing of a gene product The majority of the known mechanisms regulate the expression of protein coding genes Any event in the sequence of reactions in gene expression can serve as a regulatory step Genes are not distributed randomly in a genome Genes are not continually expressed

8. Cells organize genes and regulate their transcription This helps to conserve energy Helps to respond efficiently to environmental conditions Gene expression regulation gives a cell control over its structure and function

9. Some genes do not have to be on all the time Genes encoding proteins of basic essential function are called housekeeping genes Housekeeping genes are usually always on. This is called constitutive expression

10. GENE EXPRESSION REGULATION IN PROKARYOTES Regulation of gene expression is required to adapt quickly to the ever changing outer environment. The presence, quantity and type of nutrients determine which genes are expressed Not all genes are transcribed individually Genes associated with a particular process or pathway are often located adjacent to each other in a genome Control of transcription initiation is the predominant site for expression control

11. OPERONS In prokaryotes genes are clustered into operons An operon is a group of functional genes all transcribed from a single promoter The use of a single promoter generates polycistronic mRNA Contain structural genes and the associated regulatory genes

12. MAIN FEATURES OF AN OPERON Promoter : Sequence element on DNA that is recognized by RNA polymerase. Operator region : Usually adjacent to promoters in operons . It regulates access to the promoter by interacting with proteins. Regulatory gene : Encodes a protein that inhibits RNA polymerase (repressor) or a protein that promotes RNA polymerase binding (inducers) in response to environmental stimulus. Structural gene(s): a gene that codes for the amino acid sequence of a protein

13. THE LACTOSE OPERON

14. Regulation of the lac operon in E. coli The repressor of the operon is synthesized from the i gene. The repressor protein binds to the operator region and prevents RNA polymerase from transcribing the operon. In the presence of an inducer (e.g.allolactose) the repressor is inactivated by interaction with the inducer. Transcription occurs when the inducer is present. The resultant mRNA is polycistronic. The mRNA encodes β -galactosidase, permease and transacetylase neded to utilize β -galactosides (such as lactose) as an energy source. The lac operon is additionally regulated through binding of the cAMP-receptor protein, CRP (also termed the catabolite activator protein, CAP) to sequences near the promoter domain of the operon. The result is a 50 fold enhancement of polymerase activity.

15. Operons are either inducible or repressible according to the control mechanism Inducible system : Off unless an inducer is present to allow gene expression. Repressible system : On unless a co-repressor is present. INDUCTION AND REPRESSION

16. Many inducible operons are also controlled by the level of glucose in the environment The is called CATABOLITE REPRESSION. This usually occurs in operons involved in the degradation of compounds used as a source of energy There is an inverse relationship between glucose levels and cyclic AMP ( cAMP ) levels in bacteria cAMP binds to a protein called CAP or CRP. The cAMP -CAP complex, but not free CAP protein, binds to a site in the promoters of catabolite repression-sensitive operons The binding of the complex results in a more efficient promoter and thus more initiations of transcriptions from that promoter CATABOLITE REPRESSION

17. GENE EXPRESSION IN EUKARYOTES Transcription and translation are separated in time and space. Transcription occurs in the nucleus. Translation occurs in the cytosol The primary transcripts are extensively modified in higher organism. Only a small amount of RNA synthesized in the nucleus reach the cytosol as mRNA. Most eukaryotic genes are regulated by transcriptional activation. Few eukaryotic genes are regulated by repressors. Transcription is virtually nonexistent without activators in most eukaryotic genes.

18. SEQUENCES BOUND BY ACTIVATORS Two general types of eukaryotic sequences to which activators bind are recognized. UPSTREAM ACTIVATING SEQUENCE (UAS). Found upstream of many genes coding for metabolic enzymes in unicellular eukaryotes e.g. yeast. Rate of transcription initiation for associated promoters is enhanced by activators. ENHANCER . Found in multicellular eukaryotes. Unlike UAS can be found either upstream or downstream to a gene. Can affect transcription even when located a great distance from the start site of transcription.

19. REGULATION OF EUKARYOTIC GENE EXPRESSION Like in prokaryotes, transcriptional control appears to be the major process of regulation. Eukaryotic genomes do not contain operons that give rise to polycistronic mRNAs. Eukaryotic genes whose products are required for the same metabolic pathway, at the same time during development or in similar tissues are often arranged as gene clusters. Condensation or decondensation can be used to coordinately regulate clustered genes.

20. regulation of expression contd Eukaryotic cells of animals also show enzyme induction in response to specific substrates and certain hormones. Enzyme induction and repression in vertebrates occur mostly in the liver and epithelial cells of the small intestine. This is probably an adjustment mechanism to nutritional intake. Some hormones bind to receptor proteins forming complexes that bind to specific sites in the chromatin and promote the transcription of certain genes. cAMP and cGMP probably function by binding to receptor proteins which in turn modulate the transcription of certain genes in the chromatin.

21. NON TRANSCRIPTIONAL CONTROL In addition to transcriptional control, differential expression can be brought about by nontranscriptional regulatory mechanisms.

22. NON TRANSCRIPTIONAL CONTROL The areas of control include: Chromatin structure Transcript processing and modification RNA transport Transcript stability Post translational modification Protein transport Control of protein stability

23. TRANSLATIONAL CONTROL Gene expression can also be regulated by controlling mRNA translation. The control of translation initiation is used to regulate protein production in both prokaryotes and eukaryotes. Translational control is generally used to regulate the production of proteins that assemble into multisubunit complexes or proteins whose expression in the cell must be strictly controlled to maintain viability.