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Ch 11- Controlling Gene Expression • • • • • • • • • • • • • • • Activator Adult stem cells Alternative RNA splicing Carcinogens Clones Differentiation Embryonic stem cells Enhancers Gene expression Histones Homeoboxes Homeotic gene Nuclear transplantation Nucleosome Oncogene • • • • • • • • • • • • • • Operator Operon Promoter Proto-oncogene Regeneration Regulatory gene Repressor Reproductive cloning Signal-transduction pathway Silencers Therapeutic cloning Transcription factors Tumor-suppressor gene X chromosome inactivation What is gene expression? • Process by which genetic information flows from genes to proteins (genotype to phenotype) – Interaction of proteins and DNA turn prokaryotic genes “on” and “off” – Genes that are turned “on”- are being transcribed into RNA and translated into proteins (being expressed) – Turning a gene “on” or “off” controls the expression of certain genes (expressed as proteins) in a cell Example: • E. coli – bacteria – regulates gene expression by environmental changes – lac operon- when lactose is present= cell needs to produce protein to break it down and use it • When lactose is absent= doesn’t want to bother making the protein to break down lactose – Promoter- site where RNA pol attaches – Operator- site that determines whether promoter can bind or not to RNA pol – Promoter + operator + genes to be transcribed = operon – Repressor- protein that binds to operator; blocks transcription – Regulatory gene- outside of operon; codes for repressor; always expressed • Repressor will only bind if certain molecules are present (fits into repressor) – Activators- proteins that turn operon “on” by binding to DNA • Makes RNA pol bind more easily Cell differentiation produces variety • Differentiation- cells become specialized in structure and function – Results from selective gene expression – Doesn’t cause change in DNA – Ex: muscle contraction protein gene: turned on in muscle cells, off in RBC’s – Differentiated cells maintain genetic potential • Plant cells can dedifferentiate and give rise to a new plant • Regeneration- body part can be re-grown Carrot cloning Clones and cloning • Clone- genetically identical organism • Nuclear transplantation- nucleus of an egg is replaced with body cell nucleus • Cloning in the news: – Reproductive • Helps in research, agriculture, medicine – Therapeutic • Embryonic stem cells- can give rise to any specialized body cells; immortal in a culture Controlling gene expression in eukaryotes • How DNA is packaged – Histones- small proteins; helps coil DNA – Nucleosome- “bead” consisting of 8 histones and DNA wound around it – String of “beads” is then coiled, which is then coiled on itself – Packaging prevents RNA pol from reaching DNA – Histones must loosen grip on certain part of DNA, then RNA pol may bind to DNA Example of how DNA packaging effects gene expression: • X-inactivation – In female mammals, 1 X chromosome is so tightly compacted that it is inactive, even during interphase – Initiated early in embryonic development – A random event – Heterozygous females on X chromosome will express different X-linked alleles – Ex: tortoiseshell cat Complex proteins control eukaryotic transcription • More regulatory proteins and control sequences in eukaryotes • Each gene has its own promoter and control sequence • Activators are more important than repressors usually (default is “off”) – Except for activities that must happen continuously, Ex: glycolysis, their default is “on” Complex proteins control eukaryotic transcription • Transcription factors- regulatory proteins that turn on eukaryotic transcription (in addition to RNA pol) – Activators are one type that bind to enhancer DNA sequences; sequences that regulate far from gene – DNA bends and TF’s bind to create an area where RNA pol can bind to – Silencers- are sequences that repressors bind to; stop transcription initiation • Coordinating gene expression- eukaryotes rarely have operons, so enhancer sequences and transcription factors are important for the transcription of genes Expression is also regulated by alternative RNA splicing • RNA can be spliced differently to yield different polypeptides from the same gene • Ex: sex of fruit flies • Can also affect when mRNA molecules move into cytoplasm Translation and even proteins can also be regulated • mRNA breakdown- Determines how many proteins are made – In prokaryotes- mRNA breaks down quickly – In eukaryotes can last much longer • Initiation of translation- proteins are in place to control the start of translation; sometimes determined by available chemicals • Protein activation- polypeptides are cleaved to yield smaller active protein • Protein breakdown- selective breakdown; response to change in environment Genetic Control of Embryonic Development • Gene expression can determine body plan – Concentration gradients of mRNA and proteins determine body layout – Homeotic gene- master control gene; regulates genes that determine body plan – Many proteins act as signals to notify bordering cells • Within homeotic genes there are sequences that are very similar between all eukaryotes – Homeoboxesnucleotide sequences that code for part of a protein that can bind to the DNA of the gene that it regulates • Signal transduction – Series of molecular changes that converts a signal on the cell surface to a response within the cell • Cell to cell signaling • Uses relay of proteins to initiate transcription Genetics behind cancers • Oncogene- gene that causes cancer • Proto-oncogene- normal gene that has the potential to become an oncogene – Many code for growth factors (stimulate cell division) – Can become oncogenes a few ways – Mutation, having multiple copies of gene, movement of gene to new location with new controls • Tumor-suppressor genesproduces proteins that prevent uncontrolled cell division • If there is a mutation a cell might start to divide excessively • Figure 11.15B in chapter • Oncogene proteins and faulty tumorsuppressor proteins can affect signal transduction pathways – Oncogene protein can be hyper active and stimulate cell division – Tumor-suppressor protein can stop protein that inhibits cell division from being produced • Cancer does not usually start from 1 mutation in a somatic cell – Oncogene can be activated then tumor-suppressor genes can be inactivated (usually more than 1 is), this possibly produces a tumor – An accumulation of mutations in a lineage of somatic cells can cause a malignant cell • Avoiding carcinogens can reduce risk – Carcinogen- factors that alter DNA and make cancerous cells • Ex: X-rays, UV light, tobacco (chemicals), • When something can cause a mutation in DNA it runs a risk of affecting the cell division control system