mitosis Gene Regulation A. Overview All cells in an organism contain the same genetic information; the key to tissue specialization is gene regulation – reading some genes in some cells and other genes in other cells. zygote mitosis

C. Regulation of Protein Synthesis 1. Regulation of Transcription a. CHROMOSOME ARCHITECTURE - DNA bound to histones can’t be accessed by RNA Polymerase - but the location of histones changes, making genes accessible (or inaccessible) Initially, the orange gene is “off”, and the green gene is “on” Now the orange gene is “on” and the green gene is “off”.

C. Regulation of Protein Synthesis 1. Regulation of Transcription a. CHROMOSOME ARCHITECTURE b. Proteins that REPRESSOR or INDUCE transcription Promoter 3’ 5’ sense A C T A T A C G T A C A A A C G G T T A T A C T A C T T T T G A T A T G C A T G T T T G C C A A T A T G A T G A A A nonsense 5’ 3’ exon intron exon RNA POLY Proteins can inhibit or encourage the binding of the RNA Polymerase. And, through signal transduction, environmental factors can influence the activity of these proteins. So cells can respond genetically to changes in their environment.

Genes for splitting lactose into glucose and galactose are OFF Escherichia coli (E. coli) bacteria Glucose present: Genes for splitting lactose into glucose and galactose are OFF Glucose absent, lactose present: Genes for splitting lactose into glucose and galactose are ON How do they know?? : ))

C. Regulation of Protein Synthesis 1. Regulation of Transcription a. CHROMOSOME ARCHITECTURE b. Proteins that REPRESSOR or INDUCE transcription: LAC OPERON example OPERON: genes that are regulated as a unit typically encodes > 1 protein involved in a particular metabolic pathway. Common in bacteria; less so in eukaryotes. LAC operon: encodes three enzymes involved in absorption, metabolism, and detoxification of lactose sugar.

The lac Operon in E. coli - Effects of lactose (if glucose absent): 1) In absence of lactose: Repressor Gene Operator (RNA poly) Repressor RNA Poly

The lac Operon in E. coli - Effects of lactose (if glucose is absent): 1) In absence of lactose: 2) In the presence of lactose: LACTOSE The binding of lactose changes the shape of the repressor (allosteric reaction) and the repressor can’t bind to the operator.

VII. Gene Regulation C. The lac Operon in E. coli D. Summary These are the transcription factors that bind to enhancer and repressor regions of the human metallothionien IIA gene promoter region!! - What does having all these modifiers allow for?

VI. Protein Synthesis A. Overview B. The Process of Protein Synthesis C. Regulation of Protein Synthesis 1. Regulation of Transcription 2. Transcript Processing intron exon Initial RNA PRODUCT: G C A U GUUU G C C A A U A UG A C C C… Proteins can bind to m-RNA and change splicing patterns. This can turn protein synthesis off completely …. (here, a UGA is retained and stops synthesis prematurely…..)

VI. Protein Synthesis A. Overview B. The Process of Protein Synthesis C. Regulation of Protein Synthesis 1. Regulation of Transcription 2. Transcript Processing Or, a different combination of exons are spliced together…resulting in DIFFERENT PROTEINS produced from the SAME GENE. A calcium regulator in the thyroid Initial m-RNA A hormone made in the brain

VI. Protein Synthesis A. Overview B. The Process of Protein Synthesis C. Regulation of Protein Synthesis 1. Regulation of Transcription 2. Transcript Processing Ds-RNA intron exon Initial RNA PRODUCT: G C A U GUUU G C C A A U A UG A U G A… C G G U Or, micro-RNA’s (mi-RNA’s) can bind to the m-RNA. These are recognized by other enzymes and are cleaved incorrectly, Or simply block the ribosome from translating the sequence.

VI. Protein Synthesis A. Overview B. The Process of Protein Synthesis C. Regulation of Protein Synthesis 1. Regulation of Transcription 2. Transcript Processing 3. Regulating Translation 4. Regulating Post-Translational Modification Meth Phe Ala Asn The patterns of cleavage and modification can vary.

PROCESS REGULATION GENE In DNA Transcription: DNA is read RNA is made Chromosome architecture or protein binding enhances or represses RNA polymerase activity 2) RNA Splicing: Introns cut out exons spliced together Proteins binding to sites may enhance or inhibit spliceosome and change splicing pattern 3) Translation: Amino acids joined based on codon sequence in m-RNA mi-RNA binding may stimulate incorrect splicing and m-RNA destruction, or block ribosome: no protein produced either way 4) Post-translational Processing: Protein spliced; molecules added Other enzymes present determine how the protein is modified PROTEIN

REGULATION OF GENE ACTIVITY What genes are on (transcribed)? - chromosome architecture: folding of chromosome and histone arrangement - inducers and repressors from inside and outside the cell/organism What protein, if any, is made? - transcript splicing patterns - mi-RNA interference - post-translational modification Feedback Loops and Interactive Effects - What effect does this protein have on the activity of this and other genes?