Chapter 18 Lecture notes Prokaryote Gene Regulation: Bacterial cells control metabolism by regulating enzyme activity or the expression

of genes coding for enzymes. Operon: cluster of related genes, a promoter, an operator, and a repressor protein. Negative Gene Regulation Two types: repressible, inducible o Both are examples of negative gene regulation (specific repressor protein to the operator shuts off transcription) Repressors/Inducers: o Encoded by a separate regulatory gene (not part of the operon) o Repressible operon (trp) repressor needs a corepressor to be active (usually the end product of an anabolic pathway) o Inducible operon (lac)an inducer binds to an always active repressor to inactivate it and turn on transcription. INDUCIBLE ENZYMESCatabolic (breaking down lactose) REPRESSIBLE ENZYMESAnabolic (building tryptophan) Positive Gene Regulation E. coli prefers glucose over lactose Enzymes for glucose breakdown are continually present in cell. Only if glucose is in short supply does it use lactose for energy. (I prefer sprite over sierra mist, so only if the drive thru doesnt have sprite will I get sierra mist.)

Sensing low levels of glucose: cAMP starts to accumulate when glucose is scarce Higher levels of cAMP make it more likely it will bump into CAP (catabolite activator protein) They bind together and CAP knows its time to do its job: bind to DNA and stimulate gene transcription. Flags RNA polymerase to the lac operon (because it normally likes the glucose pathway) Why is it considered positive? CAP promotes continuous breakdown of lactose SO the lac operon has BOTH positive and negative regulation:

Negativelac repressor protein (controls rate of transcription) Eukaryotic Gene Expression

(turns transcription on or off) PositiveCAP

Differential Gene Expression: basically it means that we have ALL of the DNA in each of our cells however certain genes were turned on/off to make them SPECIALIZED (eye cell, nerve cell, muscle cell, fat cell, etc.) and then turn certain parts on/off depending on what FUNCTION they need to perform or respond to in both their internal and external environment. FIGURE 18.6each stage in gene expression can act as a control point and can slow down/ speed up/ turn on/turn off Regulation of Chromatin Structure Remember introns and exons? Heterochromatin/euchromatin? Histone modifications Histone tailsstick out and are available to be modified by different types of modifying enzymes that catalyze the addition or removal of various chemical groups. o Histone Acetylation: acetyl groups are added (COCH3) making chromatin looser and more readily transcribed. o Histone Methylation: methyl groups are added to tails condense chromatin. o SEE FIGURE 18.7 DNA Methylation Methylates certain bases of DNA itself Occurs in most plants, animals, and fungi OFF SWITCHES if present Same bookdifferent version of the story

EPIGENETIC INHERITANCE Although the chromatin modifications do not directly affect the DNA sequence, the modifications can be passed down to future generations of cells.

Regulation of Transcription Initiation

Once youve passed chromatin modifications, youre ready to become a protein.. right? Nope, youve got to pass the transcription initiation complex! Control Elements+Transcriptin Factors+RNA polymerase= Transcription initiation Complex Enhancers: distal control elements located upstream of the promoter that enhance transcription RATE. Transcription factors: can be ACTIVATORS or REPRESSORS that bind to enhancers. FIGURE 18.10 Post-Transcriptional Regulation Alternative RNA splicing--- are you an intron or an exon? Depending on what you are treated as, many different genes can come from the same RNA transcript. Fig 18.13 mRNA degradation-- life span of an mRNA dictates how long it will be translated in the cytoplasm. Initiation of translationcertain regulatory proteins or a too-short poly-A tail can block ribosome from binding to the mRNA. Protein processing & degradation-- Polypeptides must be processed, refined, and dressed-up before they become functional. Proteasomes recognize old proteins marked with ubiquitin and break them down. Proteins that cant be broken down by proteasomes can often lead to cancer. Non-Coding RNAs microRNAs (miRNAs)-- of all human genes are regulated by miRNAs , they block or degrade complementary mRNA sequences. RNAithe cop or now known as small-interfering RNAs (siRNAs), similar in size and function to miRNAs. Virus defenders, they turn off translation of proteins for specific genes. They can also cause remodeling of chromatin structure. 18.4: A program of differential gene expression leads to the different cell types in a multi-cell organism Differentiationprocess by which cells become specialized in structure and function Organization of these cells into tissues, organs, organ systems: Morphogenesis Cytoplasmic determinants: maternal substances in the egg that influence the course of early development. Induction: growth factors, contact with other cells, and where a cell is anchored

dictates what kind of cell it will be! Once youve past a certain induction point, there is no turning back you are the cell you were destined to be! Pattern formation: cytoplasmic determinants & inductive signals contribute to the formation of a body plan. Segmented arthropods make great specimens to study pattern formation: what part of the larvae will become the head, thorax, & abdomen? See fig 18.19 How do we do all this magic of development??? HOMEOTIC GENES OF COURSE!!! Axis establishment: accomplished by cytoplasmic determinants, encoded for by maternal effect genes. If you mutate these, your embryo will be mutatedeven if the embryos genes are completely normal! They are also called egg-polarity genes. CANCER!!! Oncogenes-- cancer-causing genes. (onco means tumor in greek), they used to be proto-oncogenes and were completely normal, until a genetic change occurs that triggered them into becoming oncogenes. Tumor-Suppresor genesproteins that they encode help prevent uncontrolled cell growth. They are regularly present in the body, and if something happens to their expressioncancer may occur. This is why you may develop cancer due to environmental factors everything you are exposed to has the possibility of turning a proto-oncogene into an oncogene, OR turn off or inactivate tumor-suppresor genes!