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

– 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