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

Essential aa so needs to make it when not available

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 Can study the effects of changing genes, clone farm animals with desirable traits, clone animals that produce valuable drugs (Ex sheep that secrete human blood protein in their milk) Therapeutic- produce human organs in animals

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 http://www.eht.k12.nj.us/~dannenhm/Honors%20Web%20Folder/Notes%20for%20website/Ch.%2015%20Notes.htm

Within homeotic genes there are sequences that are very similar between all eukaryotes Homeoboxes- nucleotide 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 genes- produces 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 tumor-suppressor 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