This document discusses various levels of gene regulation in prokaryotes and eukaryotes. It explains that genes can be regulated at the structural, transcriptional, post-transcriptional, translational, and post-translational levels. In eukaryotes, regulation occurs through promoters, enhancers, repressors, and other transcriptional and post-transcriptional mechanisms like alternative splicing, microRNAs, and RNA interference. Gene expression is controlled by combinatorial interactions between regulatory proteins, chromatin remodeling, and accessibility of DNA sequences.
This document discusses various levels of gene regulation in prokaryotes and eukaryotes. It explains that genes can be regulated at the structural, transcriptional, post-transcriptional, translational, and post-translational levels. In eukaryotes, regulation occurs through promoters, enhancers, repressors, and other transcriptional and post-transcriptional mechanisms like alternative splicing, microRNAs, and RNA interference. Gene expression is controlled by combinatorial interactions between regulatory proteins, chromatin remodeling, and accessibility of DNA sequences.
This document discusses various levels of gene regulation in prokaryotes and eukaryotes. It explains that genes can be regulated at the structural, transcriptional, post-transcriptional, translational, and post-translational levels. In eukaryotes, regulation occurs through promoters, enhancers, repressors, and other transcriptional and post-transcriptional mechanisms like alternative splicing, microRNAs, and RNA interference. Gene expression is controlled by combinatorial interactions between regulatory proteins, chromatin remodeling, and accessibility of DNA sequences.
This document discusses various levels of gene regulation in prokaryotes and eukaryotes. It explains that genes can be regulated at the structural, transcriptional, post-transcriptional, translational, and post-translational levels. In eukaryotes, regulation occurs through promoters, enhancers, repressors, and other transcriptional and post-transcriptional mechanisms like alternative splicing, microRNAs, and RNA interference. Gene expression is controlled by combinatorial interactions between regulatory proteins, chromatin remodeling, and accessibility of DNA sequences.
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Promoters, Activators, Enhancers, Mediators
GENE CONTROL ELEMENTS
GENES AND REGULATORY ELEMENTS Structural genes proteins used in metabolism or biosynthesis Regulatory genes products are either RNA or proteins, interact with other sequences and affects transcription and translation. Regulatory elements expression of sequences to which they are physically linked.
LEVELS OF REGULATION 1) Alteration of gene structure modification to DNA, its packaging - DNA methylation, changes in chromatin 2) Transcription 3) mRNA processing - Eukaryotic mRNA modified -5 cap, 3 end polyadenlyated, introns removed. - Determines : - Stability of mRNA, whether mRNA can be translated, the rate of translation, and the amino acid sequence. - Growing evidence that eukaryotic cells operate at the level of mRNA processing 4) Regulation of RNA stability rate of synthesis and degradation. 5) Translation complex process requiring large number of enzymes, protein factors, and RNA molecules. 6) selectively activating or inactivating proteins after they have been made.
LEVEL OF REGULATION - EUKARYOTES TRANSCRIPTIONAL LEVEL Promoters include an initiation site 50 nucleotides upstream a sequence for binding of RNA polymerase Regulatory DNA sequences are used to switch the gene ON and OFF. In bacteria 10 nucleotide pairs long In eukaryotes - >10,000 sequences molecular microprocessors integrating information Regulatory DNA sequences must be recognized by proteins called transcription regulators
Proteins inserts into major grooves of DNA helix.
Proteins form hydrogen bonds, ionic bonds, hydrophobic interactions with the edges of the bases. Fits into the DNA in the form of dimers. Dimerization doubles the area of contact with the DNA ensures only limited number of proteins have access to the DNA
GENES SWITCHED ON AND OFF Repressor proteins in its active form, switched off the gene or represses it. Promoters are able to marginally bind and position RNA polymerase Activator proteins enhances the promoter by binding to a nearby DNA site and contact RNA polymerase to initiate transcription. - Able to bind to another molecule before binding with DNA. EUKARYOTIC TRANSCRIPTIONAL REGULATORS Both activators and repressors to regulate the expression of genes. Enhancers Regions of DNA where eukaryotic gene activators are bound. Activators enhance transcription even when bound thousands of nucleotides away from genes promoters. DNA between enhancer and promoter loops out allowing protein bound to an enhancer to interact with the proteins in the vicinity of the promoter. Mediators large complex proteins aiding in the assembly of the general transcription factors and RNA polymerase at the promoter. Eukaryotic transcription regulators attract proteins that modulate chromatin structure and thereby affect the accessibility of the promoter
PACKING OF PROMOTER DNA Nucleosomes highly folded structures of DNA. Can inhibit transcription if positioned over promoter, because it blocks the assembly of the general transcription factors RNA polymerase. Chromatin structure altered by - chromatin remodeling complexes and - Enzymes that covalently modify histone proteins - Gene activators recruits histone acetylases attach an acetyl group to lysine tail of histone proteins greater accessiblity to DNA.
Gene repressor proteins modify chromatin to reduce efficiency of transcription initiation. Repressors attract histone deacetylases removes acetyl groups from histone tails reversing the effects. COMBINATORIAL CONTROL OF EUKARYOTES Combinatorial control refers to the way that groups of regulatory proteins work together to determine the expression of a single gene.
Specialized cells differentiate into a specific cell type and cell memory is a prerequisite for the creation of organized tissues.
A mammalian skeletal muscle cell is a highly distinctive cell type. Large cell formed by fusion of many muscle precursor cells myoblasts distinguished by the presence of actin, myosin, receptor proteins, ion channel proteins in the cell membranes. Genes encoding these muscle specific proteins are all switched on coordinately as the myoblasts fuse.
POST-TRANSCRIPTIONAL CONTROLS Operate after RNA is synthesized. Alternative splicing Self- regulating mRNA have -riboswitches - Short sequences of RNA that change their conformation when bound to small molecules. - Economical, because they bypass the need for regulatory proteins. - UTR can control translation ribosome recognition forms base pairs with the RNA in the small ribosome subunit ideal target for translational control.
Eukaryotes 5cap helps guide the ribosome to AUG. Repressors can inhibit translation initiation by binding to the specific sequences in 5UTR. microRNA (miRNA) non coding RNA found in plants and animals. - regulates protein coding genes. - control gene expression by base-pairing with specific mRNAs. MiRNA is assembled with specialized proteins to form an RNA-induced silencing complex RISC Searches for target mRNA in the cytoplasm base pairs regions in 5 and 3 UTR- mRNA destroyed by nuclease.
RNA interference (RNAi): Viruses and transposable genetic elements produce dsRNA. Targeted RNA degradation mechanism helps to keep these potentially dangerous invaders in check. dsRNA triggers RNAi by attracting protein complex containing nuclease - Dicer
Dicer cleaves dsRNA intro short fragments and sends to RISC. RISC discards one strand and with another strand searches for complementary foreign RNA molecule. RNA I activity can spread from tissue to tissue by movement of RNA between cells.
