Regulation of Gene Activity and Gene Mutations

Mader- Chapter 15

Prokaryotic Regulation

• The Operon Model– Structural genes are controlled by upstream

operator DNA than can bind a repressor molecule which prohibits RNA polymerase from binding to the promoter region of DNA

Repressible vs. Inducible Operons-Two types of gene control

trp Operon• Repressible operon (on unless turned off)• The gene for anabolizing tryptophan is turned

off in the presence of the amino acid tryptophan

• Negative gene control• Why waste energy?

lac Operon• Inducible operon (off unless turned on)• The gene for catabolizing lactose is turned

on in the presence of the sugar lactose• Positive gene control• Why waste energy?

Virtual Cell lac Operon Movie

Further Positive Gene Regulation through “CAP” Catabolic activating protein

• When glucose levels are low then cAMP is high• cAMP acivates CAP• CAP binds to promoter and enhances binding of RNA Polymerase

lac Operon

Eukaryotic Regulation5 Levels of Eukaryotic Gene Regulation

1. Chromatin Structure-Does RNA Polymerase have access to the gene

2. Transcriptional Control-transcription factors, activators, and the presence or absence of transposons

3. Posttranscriptional Control-RNA processing

4. Translational Control- Does tranlation take place and for how long?

5. Post Translational Control- Activation of the protein itself

Chromatin Structure

Acetylation (-COCH3) opens up the DNA for transcription but Methylation (-CH3) of the tails shuts it down

One of my X chromosomes is shut

down through methylation in every

cell… meow!

Odd cases of Bilateral GynadromorphismAn early mistake during mitosis incorrectly

separates the X and Y chromosome creating an organism that is half male and half female!

Transcriptional Control in Eukaryotes

Transcription Factors and Activators

•Transcription Factors- There are many types… these proteins bind to the promoter and help RNA polymerase bind•Transcription Activators- bind to an upstream Enhancer region and also promote transcription

Transposons “Jumping Genes” are noncoding sections of DNA that can also insert themselves into the structural gene and effectively turn them off

Post Transcriptional Control- mRNA Editing

It is not well understood how cells determine which form of mature mRNA that they will make but it is clear that the one gene to one protein theory is simply not true.

It was found that one gene in Drosophilia is alternatively spliced ~17,500 different ways which all become cell surface proteins that identify placement of neurons in the organism

Translational Control

• The 5’ methylated cap and the 3’ poly A tail determine “If” and “for how long” will translation occur.

• Also, research is being done to discover how introns are feeding back to regulate translation of mRNA

Effects on mRNA by MicroRNAs and Small Interfering RNAs

• miRNAs and siRNAs are very similar

• Both begin double stranded and then degraded to single stranded

• Both bind to mRNA of complimentary sequence to attract a degrading protein

• Degradation of mRNA silences the gene

Post Translational Control

• Lastly, cells control how long a protein will remain active. Cells have many proteases for degrading and breaking down old protein.

Development: How do we get from zygote to organism?Ectoderm nervous system,

Epidermis, mammary glands, enamel of the teeth

Mesoderm connective tissue, cartilage, and bone; muscles; the heart walls, blood and lymph vessels and cells; the kidneys; the gonads (ovaries and testes) and genital ducts; the spleen; and the suprarenal (adrenal) cortices

Endoderm gastrointestinal and respiratory tracts, the liver, the thymus, the thyroid, the parathyroids, and the pancreas; the epithelial lining of the urinary bladder and urethra

From zygote to tadpole to frog; How does this happen?

1. The unfertilized egg is not homogenous in respects to mRNA and proteins; these are known as cytoplasmic determinants that begin differentiation

2. Indeterminate and determinate clevage. Cells resulting from determinate clevage will not be able to become a completer organism because they are destined to be a specific portion of the organism

3. Changing cells send signals to nearby cells causing change; this is termed induction

4. Positional information from steps 1 and 2 creates pattern formation of body axes by influencing homeotic genes

5. Apoptosis; or programmed cell death refines the tissue. Apoptosis rids the tadpole of its tale and removes the webbing between a humans digits.