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ISU BBMB 405 - Major Groove
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BBMB 405 1st Edition Lecture 37Outline of Last Lecture XVII. Chapter 31: The control of gene expression in prokaryotesA. Gene expression can be controlled at posttranscriptional levelsXVIII. Chapter 32: The control of gene expression in eukaryotesA. Eukaryotic vs Prokaryote transcriptional regulationB. Eukaryotic DNA is organized into chromatinC. The control of gene expression can require chromatin remodelingOutline of Current Lecture XVII. Chapter 32: The control of gene expression in eukaryotesC. The control of gene expression can require chromatin remodelingD. Transcription factors bind DNA and regulate transcription initiationCurrent LectureXVII. Chapter 31: The control of gene expression in prokaryotesC. The control of gene expression can require chromatin remodeling1. Nuclear hormone receptors (NRs): a class of transcription factorsa. Estrogen receptor is an example of nuclear hormone receptorsb. Cholesterol-derived steroid hormone, can diffuse across membrane because hydrophobic then activated to bind to DNA 2. Nuclear hormone receptors recruit co-activatorsThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.a.b. Helix 12 is an activation helixc. Agonist: chemical that binds receptor and induces biological responsed. Unlike lac repressor, ligand binding does not alter DNA binding by estrogen receptore. Ligand binding induces co-activator bindingf. Co-activators of nuclear hormone receptors are often chromatin remodeling enzymesg. Helix 12 in inactive conformation: co-activators can’t bind3. A specific example of transcriptional activationa. One of possible schemes involves nuclear hormone receptors (NRs)b. NRs can also interact with Mediator, example: combination control4. Posttranscriptional gene regulation by small RNAsa. In nematodes, lin-4 and lin-14 genes control developmental timingb. Lin-14 encodes for a protein and lin-4 produces small RNAc. Site in 3’-UTR of lin-14 mRNA also needed for regulation; Lin-4 RNA and lin-14 3’-UTR sites are complementaryd. The discovery of small RNA that conduct posttranscriptional regulation5. miRNAs are key players in gene regulationa. Approximately 5% of human genome encodes and produces more than 1000 miRNAsb. These miRNAs regulate about 60% of human genesc. They are important in cell and tissue developmentd. The dysfunction of miRNAs is associated with cancer, cardiomyopathies, osteoporosis and other diseasee. Important proteins in miRNA pathways: microprocessor complex and dicer, argonaute proteinsD. Transcription factors bind DNA and regulate transcription initiation1. Major groove recognition by DNA-binding proteinsa. Easier to insert alpha helixb. More chemically distinct than minor groovec. Easier to distinguish between base pairs in major groove2. Common DNA-binding motifs in eukaryotic transcription factorsa. Helix-turn-helix: alpha helix inserted into DNA major groove, attached to otherdomains that carry out actual functionb. Leucine zipper: two very long alpha helices that are supercoiled, the interactions between the leucines interlock helicesc. Zinc finger: three together can recognize different sequences and can recognize longer sequences, example is GAL4, zinc is the main structure of finger, could engineer zinc finger to recognize different DNA3. Eukaryotic transcriptional regulatory elements (review)a. Cis-acting elements: regulatory sequences affecting same moleculeb. Enhancers, CAAT and GC boxes bind regulatory transcription factorsc. Some cis-acting elements are close to promoter, some are distal4. Eukaryotic transcription factors bind directly or indirectly to RNA polymerasea. Mediator complex: conserved eukaryotic complex of 25-30 proteins, approximately 1.2 MDa in humansb. Bridges interactions between Pol II and DNA-binding transcription factors5. Cell-type specific transcription factorsa. Creatine kinase gene, specifically expressed in muscle cells; beta-galactosidaseunder control of muscle creatine kinase promoter; treatment with X-gal reveals specific muscle cells that express creatine kinase TFsb. Enhancers can be spatially close due to chromatin architecture; mediator can bridge distant enhancer sites; enhancers can be sites of chromatin remodeling6. Induced pluripotent stem cells (iPSCs)a. Pluripotency is the potential to differentiate into a specialized cellb. Pluripotency can be induced in adult cells by “turning on” four genes that are important for embryonic stem cell


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ISU BBMB 405 - Major Groove

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