BBMB 405 1st Edition Lecture 37 Outline of Last Lecture XVII Chapter 31 The control of gene expression in prokaryotes A Gene expression can be controlled at posttranscriptional levels XVIII Chapter 32 The control of gene expression in eukaryotes A Eukaryotic vs Prokaryote transcriptional regulation B Eukaryotic DNA is organized into chromatin C The control of gene expression can require chromatin remodeling Outline of Current Lecture XVII Chapter 32 The control of gene expression in eukaryotes C The control of gene expression can require chromatin remodeling D Transcription factors bind DNA and regulate transcription initiation Current Lecture XVII Chapter 31 The control of gene expression in prokaryotes C The control of gene expression can require chromatin remodeling 1 Nuclear hormone receptors NRs a class of transcription factors a Estrogen receptor is an example of nuclear hormone receptors b Cholesterol derived steroid hormone can diffuse across membrane because hydrophobic then activated to bind to DNA 2 Nuclear hormone receptors recruit co activators These 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 helix c Agonist chemical that binds receptor and induces biological response d Unlike lac repressor ligand binding does not alter DNA binding by estrogen receptor e Ligand binding induces co activator binding f Co activators of nuclear hormone receptors are often chromatin remodeling enzymes g Helix 12 in inactive conformation co activators can t bind 3 A specific example of transcriptional activation a One of possible schemes involves nuclear hormone receptors NRs b NRs can also interact with Mediator example combination control 4 Posttranscriptional gene regulation by small RNAs a In nematodes lin 4 and lin 14 genes control developmental timing b Lin 14 encodes for a protein and lin 4 produces small RNA c Site in 3 UTR of lin 14 mRNA also needed for regulation Lin 4 RNA and lin 14 3 UTR sites are complementary d The discovery of small RNA that conduct posttranscriptional regulation 5 miRNAs are key players in gene regulation a Approximately 5 of human genome encodes and produces more than 1000 miRNAs b These miRNAs regulate about 60 of human genes c They are important in cell and tissue development d The dysfunction of miRNAs is associated with cancer cardiomyopathies osteoporosis and other disease e Important proteins in miRNA pathways microprocessor complex and dicer argonaute proteins D Transcription factors bind DNA and regulate transcription initiation 1 Major groove recognition by DNA binding proteins a Easier to insert alpha helix b More chemically distinct than minor groove c Easier to distinguish between base pairs in major groove 2 Common DNA binding motifs in eukaryotic transcription factors a Helix turn helix alpha helix inserted into DNA major groove attached to other domains that carry out actual function b Leucine zipper two very long alpha helices that are supercoiled the interactions between the leucines interlock helices c 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 DNA 3 Eukaryotic transcriptional regulatory elements review a Cis acting elements regulatory sequences affecting same molecule b Enhancers CAAT and GC boxes bind regulatory transcription factors c Some cis acting elements are close to promoter some are distal 4 Eukaryotic transcription factors bind directly or indirectly to RNA polymerase a Mediator complex conserved eukaryotic complex of 25 30 proteins approximately 1 2 MDa in humans b Bridges interactions between Pol II and DNA binding transcription factors 5 Cell type specific transcription factors a Creatine kinase gene specifically expressed in muscle cells beta galactosidase under control of muscle creatine kinase promoter treatment with X gal reveals specific muscle cells that express creatine kinase TFs b Enhancers can be spatially close due to chromatin architecture mediator can bridge distant enhancer sites enhancers can be sites of chromatin remodeling 6 Induced pluripotent stem cells iPSCs a Pluripotency is the potential to differentiate into a specialized cell b Pluripotency can be induced in adult cells by turning on four genes that are important for embryonic stem cell function
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