Gene Regulation Lecture Notes PDF

Gene Regulation Importance of Regulation of Gene Expression for All Organisms Gene regulation is the key to both unicellular flexibility and multicellular specialization, and it is critical to the success of all living organisms. Prokaryotes eg: Escherichia coli It can neither seek out nourishment...

Gene Regulation Importance of Regulation of Gene Expression for All Organisms Gene regulation is the key to both unicellular flexibility and multicellular specialization, and it is critical to the success of all living organisms. Prokaryotes eg: Escherichia coli It can neither seek out nourishment when nutrients are scarce nor move away when confronted with an unfavorable environment. It makes up for its inability to alter the external environment by being internally flexible. If glucose is present, E. coli uses it to generate ATP. If there’s no glucose, it utilizes lactose, arabinose, maltose, xylose, or any of a number of other sugars. Thus, E. coli responds to environmentalchanges by rapidly altering its biochemistry. Producing all the enzymes necessary for every environmental condition would be energetically expensive. Bacteria carry the genetic information for synthesizing many proteins, but only a subset of this genetic information is expressed at any time. Multicellular eukaryotic organisms 1 Individual cells in a multicellular organism are specialized for particular tasks. Nerve cell and a kidney cell , for example, carry the same genetic instructions. The proteins produced by a nerve cell are quite different from those produced by a kidney cell. Individual cells in a multicellular organism are specialized for particular tasks. Nerve cell and a kidney cell , for example, carry the same genetic instructions. The proteins produced by a nerve cell are quite different from those produced by a kidney cell. This challenge is met through gene regulation: only a subset of genes are expressed in each cell type. Genes needed for other cell types are not expressed. The mechanisms of gene regulation were first investigated in bacterial cells, in which the availability of mutants and the ease of laboratory manipulation made it possible to unravel the mechanisms. Bacterial gene regulation clearly seemed to differ from eukaryotic gene regulation. Many aspects of gene regulation in bacterial and eukaryotic cells are recognized to be similar. Gene is any DNA sequence that is transcribed into an RNA molecule. Genes include DNA sequences that encode: 1. Proteins 2. Sequences that encode rRNA, tRNA, snRNA, and other types of RNA. Structural genes encode proteins that are used in metabolism or biosynthesis or that play a structural role in the cell. Regulatory genes are genes whose products, either RNA or proteins, interact with other DNA sequences and affect the transcription or translation of those sequences. In many cases, the products of regulatory genes are DNA-binding proteins. Bacteria and eukaryotes use regulatory genes to control the expression of many of their structural genes. However, a few structural genes, particularly those that encode essential cellular functions, are expressed continually and are said to be constitutive. Constitutive genes are therefore not regulated. Regulatory elements: DNA sequences that are not transcribed at all but still play a role in regulating genes and other DNA sequences. These regulatory elements affect the expression of sequences to which they are physically linked. 2 Regulation takes place through the action of proteins produced by regulatory genes that recognize and bind to regulatory elements. The regulation of gene expression can be through processes that: 1. Stimulate gene expression, termed positive control, 2. Inhibit gene expression, termed negative control. Negative control is more important in bacteria, Positive control is more important in eukaryotes Levels of Gene Regulation 3 Alteration of DNA or chromatin structure: Takes place primarily in eukaryotes. Modifications to DNA or its packaging can help to determine which sequences are available for transcription or the rate at which sequences are transcribed. At the level of transcription: In both bacterial and eukaryotic cells. mRNA processing: Regulatory mechanisms in eukaryotic cells These modifications determine The stability of the mRNA, Whether: the mRNA can be translated, the rate of translation, the amino acid sequence of the protein produced. The regulation of RNA stability: In both bacterial and eukaryotic cells. The amount of protein produced depends not only on the amount of mRNA synthesized, but also on the rate at which the mRNA is degraded. The level of translation: In both bacterial and eukaryotic cells. Translation is a complex process requiring a large number of enzymes, protein factors, and RNA molecules. All of these factors, as well as the availability of amino acids, affect the rate at which proteins are produced and therefore 4 Posttranslational modification: In both bacterial and eukaryotic cells. Affect whether the proteins become active DNA-Binding Proteins Much of gene regulation is accomplished by proteins that bind to DNA sequences and affect their expression. These regulatory proteins generally have discrete functional parts—called domains, (60 to 90 amino acids) responsible for binding to DNA. Within a domain, only a few amino acids actually make contact with the DNA. These amino acids (most commonly asparagine, glutamine, glycine, lysine, and arginine) often form hydrogen bonds with the bases or interact with the sugarphosphate backbone of the DNA. Many regulatory proteins have additional domains that can bind other molecules such as other regulatory proteins. By physically attaching to DNA, these proteins can affect the expression of a gene. Most DNA binding proteins bind transiently to DNA and other regulatory proteins. This dynamic nature means that other molecules can compete with DNA-binding proteins for regulatory sites on the DNA. Types of DNA-binding proteins On the basis of a characteristic structure, called a motif (eg: alpha helices), found within the binding domain for example: The helix-turn-helix motif, consisting of two alpha helices connected by a turn. 5 The zinc-finger motif consists of a loop of amino acids containing a zinc ion The leucine zipper is another motif found in a variety of eukaryotic binding proteins. 6 7