L19 Gene regulation in eukaryotes

L19 Gene regulation in eukaryotes - Gene regulation in...

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Unformatted text preview: Gene regulation in eukaryotes 1 Last Time ✤ Overview of eukaryotic transcription Features of an eukaryotic gene Chromatin remodeling and gene regulation processing ✤ ✤ ✤ RNA ✤ Splicing CAP and PolyA tail modifications 2 ✤ Gene regulation in eukaryotes ✤ Proteins that affect gene transcription: Transcription Factors ✤ Classes (types) Anatomy of a transcription factor How specific transcription factors work ✤ ✤ ✤ Post transcriptional regulation: mRNA stability ✤ The role of the Poly A tail RNA interference (RNAi) 3 ✤ Many ways to regulate gene expression DNA packaging Transcription RNA processing Translation Post-translation Fig 15.1 4 Transcription factors DNA binding proteins that affect the ability of RNAP to begin transcription http://www.embl-grenoble.fr/groups/dna/t.gif 5 Two major categories of TFs ✤ ✤ General transcription factors Specific (‘regulatory’) transcription factors General TFs Specific TFs regulatory sequence core promoter 6 Specific transcription factors 1. 2. 7 Combinatorial control of gene expression ✤ ✤ ✤ Presence or functionality of Activators Presence or functionality of Repressors Modification of Activators and Repressors affect their function ✤ Chromatin condensation level 8 Anatomy of a transcription factor domains = regions of the protein with specific function http://blogs.totalpda.co.uk/wp-content/uploads/2007/10/laptop.jpg 9 Secondary structures in proteins β pleated sheet Amino acid subunits α helix 10 Classic motifs in TFs helix turn helix helix loop helix loop c re g o helix DNA-protein interaction is specific for a given sequence 11 re c he lix lix e h . turn og .h eli x Classic motifs in TFs Zinc finger Leucine zipper Zipper holds two TFs together (dimer) 12 Dimers ✤ ✤ Homodimer - two of the same protein put together Heterodimer - two different proteins put together TF TF homodimer 13 How specific transcription factors work ✤ Control RNAP (indirectly) ✤ Through interaction with TFIID interaction with Mediator ✤Through 14 Specific transcription factors interact with TFIID Activator Repressor 15 Specific transcription factors interact with Mediator Activator Repressor A R 16 Ways specific TF function can be modulated binding of effector molecule protein - protein interaction modification of TF 17 Example - glucocorticoid receptor Steroid hormones act to change gene expression Receptors are modified upon binding, travel to nucleus Control gene expression 18 Post-transcriptional regulation transcript stability conferred by the Poly A tail RNAi controls degradation of transcripts Fig 15.1 19 Not all transcripts are created equal some have short ½ lives some have very long ½ lives Length of polyA tail determines stability http://www.steve.gb.com/images/science/mrna_poly_a_tail.png 20 RNA destroying RNA? RNAi gene in plant genome cloned gene with own promoter inserted transcription occurs from both promoters - dsRNA 21 Fire and Mello (Nobel Prize 2006) RNAi No message - no protein! 22 RNAi is a common form of gene regulation in eukaryotes ✤ Benefits ✤ Precise, sequence specific post-transcriptional gene silencing Protection against certain viruses ✤ ✤ Protection against proliferation of transposons, ‘jumping genes’ 23 Summary ✤ Transcription factors (general or specific) can influence transcription initiation of RNAP ✤ TFs have domains that allow them to associate with DNA or interact with other proteins Specific TFs interact with TFIID or Mediator to control RNAP activity ✤ ✤ mRNA stability is an important contributor to overall mRNA concentration. ✤ The length of the PolyA tail can influence ½ life. RNAi can selectively degrade specific transcripts to reduce or eliminate expression 24 Ungraded problems ✤ ✤ ✤ Check out Chapter 15: S1, S4 and S5 Try Chapter 15: C2-C6, C8, C9, C28, C29, C32 Try Chapter 15: E5 25 Next Time Translation http://genome.imim.es/courses/Madrid04/exercises/ensembl/images/ribosome.jpg 26 ...
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