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Unformatted text preview: GENE REGULATION IN EUKARYOTES
CHAPTER 15 INTRODUCTION Eukaryotic organisms have many benefits from regulating their genes For example They can respond to changes in nutrient availability They can respond to environmental stresses In plants and animals, multicellularity and a more complex cell structure, also demand a much greater level of gene expression INTRODUCTION Gene regulation is necessary to ensure 1. Expression of genes in an accurate pattern during the various developmental stages of the life cycle Some genes are only expressed during embryonic stages, whereas others are only expressed in the adult 2. Differences among distinct cell types Nerve and muscle cells look so different because of gene regulation rather than differences in DNA content REGULATORY TRANSCRIPTION FACTORS Transcription factors are proteins that influence the ability of RNA polymerase to transcribe a given gene There are two main types General transcription factors Required for the binding of the RNA pol to the core promoter and its progression to the elongation stage Are necessary for basal transcription Regulatory transcription factors Serve to regulate the rate of transcription of nearby genes They influence the ability of RNA pol to begin transcription of a particular gene Regulatory transcription factors recognize cis regulatory elements located near the core promoter These sequences are known as response elements, control elements or regulatory elements The binding of these proteins to these elements, affects the transcription of an associated gene A regulatory protein that increases the rate of transcription is termed an activator The sequence it binds is called an enhancer A regulatory protein that decreases the rate of transcription is termed a repressor The sequence it binds is called a silencer Structural Features of Regulatory Transcription Factors Transcription factor proteins contain regions, called domains, that have specific functions One domain could be for DNA-binding Another could provide a binding site for effector molecules A motif is a domain or portion of it that has a very similar structure in many different proteins The recognition helix recognizes and makes contact with a base sequence along the major groove of DNA Hydrogen bonding between an -helix and nucleotide bases is one way a transcription factor can bind to DNA Composed of one -helix and two -sheets held together by a zinc (Zn++) metal ion Two -helices intertwined due to leucine motifs Alternating leucine residues in both proteins interact ("zip up"), resulting in protein dimerization Note: Helix-loop-helix motifs can also mediate protein dimerization Homodimers are formed by two identical transcription factors; Heterodimers are formed by two different transcription factors Enhancers and Silencers The binding of a transcription factor to an enhancer increases the rate of transcription This up-regulation can be 10- to 1,000-fold The binding of a transcription factor to a silencer decreases the rate of transcription This is called down-regulation 5'GATA3' Many response elements are orientation independent or bidirectional They can function in the forward or reverse orientation Most response elements are located within a few hundred nucleotides upstream of the promoter However, some are found at various other sites Several thousand nucleotides away Downstream from the promoter Even within introns!
3'CTAT5' 5'TATC3' 3'ATAG5' Regulation through TFIID and Mediator Most regulatory transcription factors do not bind directly to RNA polymerase Two common protein complexes that communicate the effects of regulatory transcription factors are 1. TFIID 2. Mediator A general transcription factor that binds to the TATA box Recruits RNA polymerase to the core promoter Transcriptional activator recruits TFIID to the core promoter and/or activates its function Thus, transcription will be activated Transcriptional repressor inhibits TFIID binding to the core promoter or inhibits its function Thus, transcription will be repressed STOP 1. Transcriptional activator stimulates 1 2. Transcriptional repressor inhibits the function of mediator This enables RNA pol to form a preinitiation complex It then proceeds to the elongation phase of transcription the function of mediator Transcription is repressed III. Recruit proteins to the promoter region to effect chromatin compaction. Regulation of Regulatory Transcription Factors There are three common ways that the function of regulatory transcription factors can be affected 1. Binding of an effector molecule 2. Protein-protein interactions 3. Covalent modification The transcription factor can now bind to DNA Formation of homodimers and heterodimers Steroid Hormones and Regulatory Transcription Factors Regulatory transcription factors that respond to steroid hormones are termed steroid receptors The hormone actually binds to the factor The ultimate effect of a steroid hormone is to affect gene transcription Steroid hormones act as signaling molecules produced by endocrine glands Secreted into the bloodstream Then taken up by cells Steroid Hormones and Regulatory Transcription Factors Cells respond to steroid hormones in different ways Glucocorticoids These influence nutrient metabolism in most cells They promote glucose utilization, fat mobilization and protein breakdown Gonadocorticoids These include estrogen and testosterone They influence the growth and function of the gonads Heat shock protein Heat shock proteins leave when hormone binds to receptor Formation of a homodimer Nuclear localization Sequence is exposed Glucocorticoid Response Elements These function as enhancers Transcription of target gene is activated The CREB Protein The CREB protein is another regulatory transcriptional factor functioning within living cells CREB is an acronym for cAMP response element-binding CREB protein becomes activated in response to cellsignaling molecules that cause an increase in cAMP Cyclic adenosine monophosphate The CREB protein recognizes a response element with the consensus sequence 5'TGACGTCA3' This has been termed a cAMP response element (CRE) Could be a hormone, neurotransmitter, growth factor, etc. Acts as a second messenger Activates protein kinase A Phosphorylated CREB binds to DNA and stimulates transcription Unphosphorylated CREB can bind to DNA, but cannot activate RNA pol The activity of the CREB protein ...
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This note was uploaded on 05/02/2008 for the course CELL 211 taught by Professor Dotson during the Spring '07 term at Tulane.
- Spring '07