Unit 11 - Gene Expression

Gene Expression

The determination of the amount and type of exact proteins in a cell at a given time.

Gene Expression includes

• if a gene gets read or not

• how transcript is spliced

• how long transcript will last in the cytoplasm

• how many times transcript will be translated

• is the transcript be translated right away or delayed

• how the protein is modified after its made

• when the protein is activated (if made initially in the wrong shape)

• how long the protein lasts before being destroyed

Why do cells need to control gene expression?

• Different stages of development

• Differentiation

• Change during the cell cycle

• Meet demands of the organ

• Respond to changing environment

• Respond to outside signals

• Make sure you are not wasting energy making things you don’t need

Epigenetics

• Epi means on top of

  • epigenetics means on top of the genome

• It involves several types of signals that either loosen or tighten the DNA 

• If the DNA is super tight (not as tight as in chromosomes) it cannot be read

• Remember that DNA can only be read in G1 and G2 anyway, so DNA is in chromatin form at this time

Euchromatin

true chromatin that isn’t methylated and is loose enough to be read

Heterochromatin

super tight highly methylated chromatin

How do epigenetics work?

• Methyl groups added to the DNA make it tighten and make it unreadable – the more methyl groups on an area of DNA, the less readable – RNA polymerase II can’t get in to make an mRNA copy.

• How does the cell know where to put the methyl groups in any given cell at any give time?  Enzymes add other tags to the DNA based on signals received that tell the methylating enzymes where to add the methyl groups.

• Acetyl groups can be added to the histone proteins, causing the DNA to unattach from the histones and unwind and loosen allowing a gene to be read

When do epigenetic patterns get added to DNA?  When can gene expression change?

• Most epigenetic patterns get wiped off in the sperm and egg

• This makes sense because the zygote cell has to be able to divide and then each cell needs an epigenetic pattern to make it a certain type of cell.

• In about 80 genes, the genes are methylated while in the sperm and egg – this is called imprinting.  That means a gene inherited from the egg will have a different methylation pattern than that same gene inherited from the sperm

• Example – same mutated gene inherited from the father – Prader Willi, from mother – Angelman’s

When are genes methylated to control gene expression?

• Methylation tags added during embryonic development to help cells become specific types (e.g., neuron vs. muscle), even though all cells have the same DNA.

• Mom’s diet affects methylation — like in mice where certain foods turned off the agouti gene.

• Early life experiences can change methylation, like rat pups getting licked more → demethylated GR gene → more relaxed for life.

• Methylation patterns shift over time, especially during big changes like puberty or menopause → explains aging effects (e.g., hair color changes).

• Lifestyle choices (food, stress, etc.) affect methylation, which influences gene expression and long-term health.

• Some methylation patterns survive in sperm/egg, passing traits to children (transgenerational epigenetics).

• Examples:

  • Mice scared of cherry blossom smell → their babies feared it too.

  • Insects given antibiotics grew eye bristles → passed to offspring.

  • Men starved/gluttonous in puberty → sons/grandsons died decades earlier.

Foxy Gene

• 🧠 Foxo is a special gene that helps control which other genes are turned on or off inside a cell.

• 🧬 It acts like a master switch for important genes that control cell survival, repair, and stress response.

• ⚙ When Foxo is active, it tells the cell to protect itself, slow down growth, or fix damage.

• 🚨 If there's stress (like too little food or too much damage), Foxo turns on helpful genes to keep the cell safe.

• 🔒 If Foxo gets turned off, the cell might grow too fast or stop fixing itself — this can lead to aging or even cancer.

• 🌱 That’s why Foxo has such a big effect on the cell — it controls many genes that keep the cell healthy and balanced.

Activators or Repressors – Bind to Distal Control Elements

• 🚀 Activators turn genes on by boosting transcription.

• 🛑 Repressors turn genes off by blocking transcription.

• 📍 They attach to distal control elements, like:

  • Enhancers (for activators)

  • Silencers (for repressors)

• 📏 These are often far from the gene but still affect it by looping the DNA.

silencer

• 🚫 A silencer is a DNA element where a repressor binds.

• 🔕 It shuts down gene expression, like pressing a mute button.

Transcription Factors – Bind to Proximal Control Elements AND to the Promoter

• 🧩 These are proteins that help RNA polymerase know where to start.

• 🎯 They bind to:

  • Proximal control elements (close to the gene)

  • The promoter (right before the gene)

• 🔐 They’re key helpers in turning a gene on.

DNA Parts

• Proximal Control Elements:

  • 🎚 Short DNA sequences near the promoter.

  • Help fine-tune when a gene is turned on.

• Promoter:

  • 🏁 Starting line where transcription begins.

  • RNA polymerase binds here.

• Distal Control Elements:

  • 🌉 Far-away DNA sections like enhancers and silencers.

  • Still control gene activity through DNA looping.

Steroid Hormones

• Steroids bind to a cytoplasmic receptor and translocate into nucleus. 

• Steroid/receptor complex binds to DNA in upstream regulatory elements to switch on genes.

Bacterial Gene Expression

• Allows bacteria to live in a changing environment

• Operons – a whole gene unit – all genes necessary for an enzymatic pathway are  lined up behind a promoter and operator

Promoter  Operator  Genes  Term. Seq.

Bacterial Operons

• Operator – controls access to promoter for RNA polymerase

• Operator is always “on” unless a protein is bound to it

• Repressor – binds to operator and blocks RNA polymerase from binding – specific to the operon.

Repressors for Operators

• For Anabolic Operons

  • Repressible Operon

  • Product shuts off operon by activating the repressor

• For Catabolic Operons

  • Inducible Operon

  • Substrate turns on operon by deactivating the repressor

In order to read a gene, what must be true?

• It can’t be part of a nucleosome

• If it is part of a nucleosome, the histones must be acetylated

• It can’t be highly methylated

• It must be attached to the nuclear matrix

• It needs transcription factors – both specific and general – bound to the promoter and proximal control elements

• It needs activators and not repressors bond to the distal control elements

Post Transcriptional regulation of Gene expression

• RNA splicing - alternate splicing creates diff proteins from same gene

• RNA degredation - things bind to 3’ UTR controlling when mRNA gets chewed up

  • make it last longer by preventning it from chewing up, also can make it get chewed up by removing itself

• Control of translation proteins bind to the 5’ UTR and allow or block translation

• Post translational modifications - can modify protein differently in the RER to make protein diff and can change the shape later by activating a protein

• Protein degredation proteins tagged for destruction

Control of RNA Processing

Alternative Splicing – spliceosomes bind to ends of introns – identified by the specific and general mRNA sequences  that snRNP’s bind to - proteins can  bind to repress the binding of snRNP’s

• every intron has 2 snerps that identify the ends

• if you have different snerps then you splice out different introns

Transposons “Jumping Genes”

• May copy and move or just move.  May jump into a gene and disrupt it; may jump into a regulatory area and increase or decrease production of that protein

• Contains a gene for an enzyme that when expressed, cuts the gene out and inserts it somewhere else

• May contain just the gene for that enzyme or may contain additional genes

• Retrotransposons – code for RNA which is then copied into DNA and inserted somewhere else in genome

Gene Rearrangements

Example: antibodies

• Like mRNA splicing except done in embryonic cells that will become immune cells

• Done in DNA and the DNA removed is destroyed so this is gene splicing not mRNA splicing, and it is permanent

Gene Expression and Embryonic Development

• How does one cell become many types of cells?

• If it takes different signals to cause differential gene expression, how do cells make or receive different signals if they start out all the same?

• What kinds of proteins will make the biggest difference in gene expression cell to cell?

  • have to have different signals for different gene expressions

  • transcription factors are the proteins that affect gene expression the most

Embryonic Development 1

After the zygote divides – cells need to express different proteins based on location – How?

• Step #1:  Cytoplasmic Determinants – RNA and proteins distributed and anchored in the egg that signal development – when the cell divides – different cells end up with different mRNA and proteins that it got from the egg.  This leads to step 2

  • pre made proteins

  • anchored in the cells in a particular place so that when it divides its in one cell and not the other

  • whole program for your whole body is in the egg

Embryonic Development 2

After the zygote divides – cells need to express different proteins based on location – How?

• Step #2:  Induction – cells receive different signals from surrounding cells that control development (must also have diff receptors to receive the signals

  • some cells make certain messengers and some cells make certain recpetors

Embryonic Development 3

After the zygote divides – cells need to express different proteins based on location – How?

• Step #3: Turn on master regulatory genes which turn on tissue specific genes to make tissue specific proteins 

How do cytoplasmic determinants lead to steps 2 & 3

• These determinants (RNA’s and proteins) code for signals, receptors, and transcription factors (most master control genes)

• Cells will make different signals and receive different signals and turn on different genes based on what determinants they have

• The determinants a cell has is based on its location, so eventually a cell will “know” what it should be by its location.

  • signals and receptors are just as important as transcription factors

  • can make and receive different signals

• ex: fruit fly early embryonic dev.

Example Early Embryonic Development in the Fruit Fly

• mRNA of bicoid gene is anchored to cytoskeleton in anterior portion of the fruit fly egg

• after division – only the cells that will become the front of the fly make the bicoid protein (only cells that got the mRNA when the cell divided)

• front cells with bicoid protein (transcription factor) develop the front structures because the bicoid protein turns on genes to give those cells the right receptors and cause them to make the right messengers and make the right transcription factors to develop the head

• If inject the bicoid protein other places develop anterior structures in other places

Body Plan Patterning

Both cytoplasmic determinants and inductive signals help set up positional information

Homeotic/Homeobox/Hox Genes

• Are highly conserved and have same sequences within the genes called homeoboxes.  

• Code for transcription factors and are master control genes

• Hox genes found in clusters on the chromosomes

• Genes are lined up in order of what part of the body they control the formation of.

• basically determine the body plan

• “program for it” — master control genes

Oncogenes

cancer causing genes induced by viruses

Protooncogenes

promote cell division, moving through cell cycle, normal genes that become cancer causing when they are:

• mutated

• amplified

• or move into an area with an active promoter (jumping gene)

• examples- growth factors, cell cycle proteins

Proto-oncogene Example

• Ras gene – codes for a G-Protein (activated by a receptor when messenger binds and sets off a series of chemical reactions leading to increase in cell division thru the activation of transcription factors)

• Mutated Ras gene – G protein is always on even when nothing is bound to receptor

• Found in 20-25% of all human tumors

Tumor Supressor Genes - restrict  cell div, stimulate apoptosis

• Repair damaged DNA

• Control cell adhesion

• Inhibit the cell cycle

• Activate cell suicide if damage is unfixable

• Example – p53 gene (p53 mutation found in over 50% of human tumors)

  • much more like to get cancer from having p53 but p53 doesn’t cause it

In response to damage it :

• Halts the cell cycle

• Turns on DNA repair enzymes

• Activated apoptosis if damage cannot be repaired

Cancer Cells vs. Normal

Cancer cells can be identified because they look different —

• cytoskeleton misshapen

• nucleus misshapen

• The less round the nucleus, the more aggressive the cancer – therefore cancer due to messed up gene expression