* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download THE ORGANIZATION AND CONTROL OF EUKARYOTIC GENOMES
Transposable element wikipedia , lookup
Ridge (biology) wikipedia , lookup
Neuronal ceroid lipofuscinosis wikipedia , lookup
Non-coding RNA wikipedia , lookup
No-SCAR (Scarless Cas9 Assisted Recombineering) Genome Editing wikipedia , lookup
Genomic imprinting wikipedia , lookup
Epigenetics in stem-cell differentiation wikipedia , lookup
Protein moonlighting wikipedia , lookup
Epigenomics wikipedia , lookup
Minimal genome wikipedia , lookup
Long non-coding RNA wikipedia , lookup
Gene desert wikipedia , lookup
Gene therapy wikipedia , lookup
Non-coding DNA wikipedia , lookup
Epigenetics in learning and memory wikipedia , lookup
Genetic engineering wikipedia , lookup
Epigenetics of neurodegenerative diseases wikipedia , lookup
Gene therapy of the human retina wikipedia , lookup
Epigenetics of diabetes Type 2 wikipedia , lookup
Gene nomenclature wikipedia , lookup
Gene expression programming wikipedia , lookup
Genome evolution wikipedia , lookup
Cancer epigenetics wikipedia , lookup
Genome (book) wikipedia , lookup
Primary transcript wikipedia , lookup
Genome editing wikipedia , lookup
Mir-92 microRNA precursor family wikipedia , lookup
Point mutation wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
Oncogenomics wikipedia , lookup
History of genetic engineering wikipedia , lookup
Helitron (biology) wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Gene expression profiling wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Microevolution wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Designer baby wikipedia , lookup
REGULATION OF GENE EXPRESSION Chapter 18 Gene expression • A gene that is expressed is “turned on”. • It is actively making a product (protein or RNA). • Gene expression is often regulated at transcription. • Newly discovered roles of RNA in gene expression Regulation of a metabolic pathway Prokaryotic Gene Regulation • Adjust activity of enzymes already present – Often through negative feedback • Adjust production level of certain enzymes OPERONS • Regulation in prokaryotes – Operator – switch segment of DNA in promoter – Operon – the promoter, the operator, and the genes they control – Regulatory gene – long distance from gene that is regulated The trp operon: regulated synthesis of repressible enzymes trp animation trp tutorial The trp operon: regulated synthesis of repressible enzymes The lac operon: regulated synthesis of inducible enzymes lac operon animation lac operon tutorial The lac operon: regulated synthesis of inducible enzymes • Regulatory gene makes protein (repressor) that inhibits operator • Regulatory protein has inactive and active shape – Corepressor – makes repressor active – Inducer – inactivates repressor • Repressible enzymes usually used when cell makes something (ex. tryptophan) • Inducible enzymes usually used when cell breaks something down (ex. lactose) Eukaryotic Gene Regulation • Expression can be regulated at any stage • Differential gene expression – different cells in an organism express different genes from the genome • Not all genes are turned on all of the time! Opportunities for the control of gene expression in eukaryotic cells GENOME ORGANIZATION • 1.5% of DNA in humans codes for protein • 24% introns and regulatory • Most is repetitive DNA (59%) • Unique noncoding is 15% CHROMATIN • Composed of DNA and proteins called histones • Nucloesome – DNA wrapped around a histone Levels of chromatin packing Eukaryotic Regulation • At DNA level – Chromatin modification, DNA unpacking with histone acetylation (turned on) and DNA demethylation (turned off) • At RNA level – Transcription, RNA processing, transport to cytoplasm • At protein level – Translation, protein processing, transport to cellular destination, protein degradation • Regulation of transcription – Transcription factors – mediate the binding of RNA polymerase to the promoter and other regulatory proteins – Enhancers – far upstream of gene; bind to transcription factors; called distal control element Figure 19.8 A eukaryotic gene and its transcript – Not many different control elements so the combination of control elements regulates gene action • Different combos of activators (transcription factors) makes different genes turn on • Different genes can be turned on by same activator Cell-type specific transcription based on available activators DIFFERENTIAL GENE EXPRESSION = DIFFERENT CELL TYPES • Cell differentiation – process by which cells become specialized in structure and function • Morphogenesis – process that gives an organism its form (shape) • Pattern formation – development of spatial organization in which tissues and organs are in their correct places • Positional information – molecular cues that control pattern formation • Homeotic genes – control pattern formation CANCER • Oncogenes- cancer causing genes in retroviruses • Proto-oncogenes – normal genes that code for proteins that stimulate cell growth and division • Tumor suppressor genes - make proteins that help prevent uncontrolled cell growth Converting proto-oncogene into oncogene Converting proto-oncogene into oncogene • Movement of DNA within a chromosome – May place a more active promoter near a proto-oncogene (= more cell division) • Amplification of a proto-oncogene • Point mutations in control element or proto-oncogene (= more expression or makes abnormal protein that doesn’t get degraded or is more active) GENES INVOLVED IN CANCER • Ras gene – makes ras (G) protein that starts cascade reactions that initiate cell division – Mutations in Ras gene cause ~30% cancers • p53 tumor suppressor gene – “guardian of genome” – Activates p21 which halts cell cycle – Turns on genes to repair DNA – Activates suicide proteins that cause cell death (apoptosis) – Mutations in P53 gene cause ~50% cancer Multistep Model of Cancer Development • Approximately half dozen changes have to occur at the DNA level for cancer to develop. • Need at least one oncogene and loss of tumor suppressor gene(s) • Most oncogenes are dominant and most tumor suppressor genes recessive so must knock out both alleles • Typically telomerase is activated A multi-step model for the development of colorectal cancer Inherited Predisposition to Cancer • 15% colorectal cancers are inherited – Most from mutated APC gene (tumor suppressor gene) • 5-10% breast cancers are inherited – Most with mutated BRCA1 and BRCA2 – A woman with one mutant BRCA1 gene (tumor suppressor gene) has a 60% chance of getting breast cancer by age 50