Rebecca Davenport BIOL 1406 BWI 11 6 16 Ch 18 Blueprint 1 Regulation of Gene Expression a Differential Expression of Genes i Prokaryotes and eukaryotes precisely regulate gene expression in response to environmental conditions ii In multicellular eukaryotes gene expression regulates development and is responsible for differences in cell types iii RNA molecules play many roles in regulating gene expression in eukaryotes b Bacteria often respond to environmental change by regulating transcription i Natural selection has favored bacteria that produce only the products needed by that cell ii A cell can regulate the production of enzymes by feedback inhibition or by gene regulation iii One mechanism for control of gene expression in bacteria is the operon model c Operons the basic concept i A cluster of functionally related genes can be coordinately controlled by a single on off switch ii The switch is a segment of DNA called an operator usually positioned within the promoter iii An operon is the entire stretch of DNA that includes the operator the promoter and the genes that they control iv The operon can be switched off by a protein repressor v The repressor prevents gene transcription by binding to the operator and blocking RNA polymerase vi The repressor is the product of a separate regulatory gene vii The repressor can be in an active or inactive form depending on the presence of other molecules viii A corepressor is a molecule that cooperates with a repressor protein to switch an operon off ix For example E coli can synthesize the amino acid tryptophan when it has insufficient tryptophan x d Repressible and inducible operons Two types of negative gene regulation i A repressible operon is one that is usually on binding of a repressor to the operator shuts off transcription ii The trp operon is a repressible operon iii An inducible operon is one that is usually off a molecule called an inducer inactivates the repressor and turns on transcription iv The lac operon is an inducible operon v By default the trp operon is on and the genes for tryptophan synthesis are transcribed vi When tryptophan is present it binds to the trp repressor protein which turns the operon off vii The repressor is active only in the presence of its corepressor tryptophan thus the trp operon is turned off repressed if tryptophan levels are high viii The lac operon is an inducible operon and contains genes that code for enzymes used in the hydrolysis and metabolism of lactose ix By itself the lac repressor is active and switches the lac operon off x A molecule called an inducer inactivates the repressor to turn the lac operon on xi Inducible enzymes usually function in catabolic pathways their synthesis is induced by a chemical signal xii Repressible enzymes usually function in anabolic pathways their synthesis is repressed by high levels of the end product xiii Regulation of the trp and lac operons involves negative control of genes because operons are switched off by the active form of the repressor xiv e Eukaryotic gene expression is regulated at many stages i All organisms must regulate which genes are expressed at any given time ii In multicellular organisms regulation of gene expression is essential for cell specialization f Histone modifications and DNA Methylation i In histone acetylation acetyl groups are attached to positively charged lysines in histone tails ii This loosens chromatin structure thereby promoting the initiation of transcription iii The addition of methyl groups methylation can condense chromatin the addition of phosphate groups phosphorylation next to a methylated amino acid can loosen chromatin iv DNA methylation the addition of methyl groups to certain bases in DNA is associated with reduced transcription in some species v DNA methylation can cause long term inactivation of genes in cellular differentiation vi In genomic imprinting methylation regulates expression of either the maternal or paternal alleles of certain genes at the start of development g Epigenetic inheritance i Although the chromatin modifications just discussed do not alter DNA sequence they may be passed to future generations of cells ii The inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence is called epigenetic inheritance h Regulation of Transcription initiation i Chromatin modifying enzymes provide initial control of gene expression by making a region of DNA either more or less able to bind the transcription machinery i Organization of a Typical Eukaryotic Gene i Associated with most eukaryotic genes are multiple control elements segments of noncoding DNA that serve as binding sites for transcription factors that help regulate transcription ii Control elements and the transcription factors they bind are critical to the precise regulation of gene expression in different cell types j The roles of transcription Factors i To initiate transcription eukaryotic RNA polymerase requires the assistance of transcription factors ii General transcription factors are essential for the transcription of all proteincoding genes iii In eukaryotes high levels of transcription of particular genes depend on control elements interacting with specific transcription factors k Mechanisms of post Transcriptional Regulation i Transcription alone does not account for gene expression ii Regulatory mechanisms can operate at various stages after transcription iii Such mechanisms allow a cell to fine tune gene expression rapidly in response to environmental changes l RNA Processing i In alternative RNA splicing different mRNA molecules are produced from the same primary transcript depending on which RNA segments are treated as exons and which as introns
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