BSC1010- I NTRO TO B IOLOGY I K. Maltz Chapter 13

G ENE R EGULATION - T ERMS TO K NOW Gene Expression- information in a gene is turned into a functional product Gene Regulation- ability to control the gene expression Constitutive Gene- genes with relatively constant levels of expression Genes are expressed ONLY WHEN THEY ARE NEEDED

P ROKARYOTIC R EGULATION E. Coli can use several types of sugars in their metabolism, but they prefer glucose When glucose is less available, and another sugar such as lactose becomes more available they need to take advantage of it Beta-galactosidase, an enzyme that helps break down lactose, is NOT constantly expressed Genes such as the ones for the lactose transporter, lactose permease, and the beta-galactosidase enzyme will stimulate the cell to produce more of those components so they can be used When the lactose is gone, those proteins are degraded

M ORE T ERMS Regulatory transcription factors- proteins that bind to DNA and affect rate of transcription Repressors- negative control of transcription Activators- positive control of transcription Small effector molecules- binds to regulatory transcription factor Operator- regulatory region of operon Operon- genes that perform the same/related function located together Prokaryotic mRNA is polycistronic!

LAC O PERON

TRP O PERON

T HE D IFFERENCE

E UKARYOTIC R EGULATION MUCH more complex than Prokaryotic gene regulation! The difference in the appearance of cell types is due to the proteome of the individual cell Regulation can be due to development and achieved by altering transcription, or translation

W HY IS IT M ORE C OMPLEX Eukaryotic genes are monocistronic There are NO operons They are subject to combinatorial control An activator protein might help RNA polymerase start transcription A repressor protein might inhibit RNA polymerase Activators and repressors themselves are subject to regulation by effector molecules, protein-protein interaction, and covalent modification Activator proteins are necessary to change chromatin structure where the gene is located, making it easier for RNA polymerase to find and recognize the region DNA methylation inhibits transcription by preventing activators from binding or by recruiting inhibitors

A CTIVATORS This action is often enhanced by activators There can also be a coactivator involved A region of the DNA, termed the enhancer region, binds the activator and coactivator This complex attracts the mediator bound to the RNA polymerase and activates RNA Polymerase more quickly

S TRUCTURAL DNA + proteins = chromatin Sometimes the chromatin is in a closed conformation, making transcription factors unable to bind to a specific gene If chromatin is in an open conformation, transcription can take place Occasionally, an activator protein can also attract histone acetyltransferase Histone acetyltransferase attaches acetyl groups to the amino ends of histones This causes the histones to loosen their grip on the DNA

S TRUCTURAL ( CONTD.) An activator can also bind ATP-dependent- chromatin remodeling enzymes The two enzymes bound together can alter nucleosome arrangement and move the nucleosome to another location on the chromatin structure This also helps RNA polymerase recognize and bind to the DNA to be transcribed

O THER H ISTONE M ODIFICATIONS Histones can be acetylated, methylated, and phosphorylated Histones may contain sites that are recognized by other proteins to aid or inhibit transcription The histone code hypothesis states that histone modification patterns are recognized by proteins These patterns provide binding sites specific to proteins that affect chromatin structure

S TEROID H ORMONES Specific transcription activators can respond directly to steroid hormones- these are called steroid receptors Steroids are an example of small effector molecules Steroids directly affect transcription and translation of specific genes They are able to work directly on DNA by being shuttled into the nucleus of cells

S TEROID M ECHANISM

G LUCOCORTICOIDS Chaperone Glucocorticoid Nuclear Localization Signal

DNA M ETHYLATION Methyl- -CH 3 DNA Methylase- adds methyl group to DNA Promoters often have CpG islands near promoters CpG Islands that are unmethylated are located near active genes, while ones with a methyl group are located near represssed genes Methylation may either prevent binding of activators or make chromatin assume a closed conformation The methylation of the CpG islands attracts methyl CpG binding proteins that further inhibit transcription

M ETHYLATION P ROBLEM Rett Syndrome- methyl CpG binding protein is defective in nerve cells Almost exclusively in women Male copy of X chromosome usually spontaneously mutates

T RANSLATION Alternative splicing MicroRNA and Short-interfering MRNA- small RNAs that silence existing mRNAs Transcribed together and fold back to form hairpin loop Dicer splices it to 22 base pairs The remaining portion attaches to RNA-induced silencing complex (RISC) This either degrades the mRNA or inhibits translation (RNA interference) A third way is to affect translational initiation- this is seen in translation of ferritin proteins