3. Molecular Biology timeline

4. RNA polymerase complex comprised of many proteins—scaffolds that bind TATA box (orange) plus enzymatic subunits. Basic complex probably the same for all cells…how to get unique RNA output? Transcription factors/enhancers and repressors. Role in cell diversity.

5. https://www. google. com/url. url=http://www. youtube
Video of how a homeodomain transcription factor contacts DNA

6. Methods for looking at transcription.

7. RNA Seq

8. Promoter bashing
Understanding regulatory regions, tissue specific enhancers, minimal promoter, tf binding sites

9. BDNF promoters
Fig. 2. Multiple activity-regulated transcription factors contribute to inducibility of Bdnf promoter IV. The box shows spliced mRNAs (blue) encoding Bdnf transcripts driven by the eight alternative Bdnf promoters mapped onto chromosome 2 of Mus musculus (black). Boxes represent the nine exons that comprise the Bdnf gene and the thicker region of exon IX indicates the coding sequence. The gray line shows an expansion of the region just upstream of exon IV. Three calcium-response elements (CaREs) and two transcription start sites (TSSs) are indicated by the gray boxes. Transcription factors demonstrated to regulate Bdnf promoter IV are shown at their binding sites. Npas4 binding has been localized to a PAS response element just 5′ to CaRE1 in human BDNF promoter IV (Pruunsild et al., 2011) and to a region near the CaRE2 element by ChIP-Seq in mouse neurons (Kim et al., 2010). Although MEF2 has been localized to Bdnf promoter IV by chromatin immunoprecipitation, its binding elements have not yet been reported. Like the Fos promoter, Bdnf promoter IV is thought to already have the RNA polymerase II (Pol II) complex pre-bound prior to neuronal stimulation.

11. Master regulator genes

12. Mitf is a master regulator of eye development

13. There is basal transcription of so-called housekeeping genes (metabolism, protein synthesis, transcription itself) but then there is also regulated transcription—an adaptation made to external cues.

14. CREB is one of the best studied transcription factors
CREB is one of the best studied transcription factors. Regulated in numerous ways. Is this unique or do we just not know as much about the other hundreds of TFs?

15. P-CREB has higher affinity for the CRE than non
P-CREB has higher affinity for the CRE than non. CREM (modulator) effects on transcription depend on alternate splicing. A, b, g isoforms lack a glutamine-rich activating region, making hetero or homodimers containing these isoforms of CREM inhibitory on gene transcription.

16. CREB affects transcription by recruiting HATs—these acetylate histones and open up DNA for access to transcriptional machinery.

17. Two waves of transcriptional activity characterize responses to external stimuli. IE genes are first round—amplify signal by affecting transcription of many target genes.

18. Nuclear hormone receptors as transcription factors. Huge family
Nuclear hormone receptors as transcription factors. Huge family! Steroid receptors huge part.
GC released from adrenal medulla in response to stress, inflammation, etc. Mineralcorticoid (aldosterone) regulates Na transport and uptake in the kidney. Use same receptors at least two high affinity receptors. GC higher than MC, but there are mechanisms to promote MC binding when GC are high. GC are found in a complex with hsp in cytoplasm. Ligand binding disrupts hsps and gc-ligand enters nucleus.

19. GRE is an enhancer—promotes transcription
GRE is an enhancer—promotes transcription. Can be found anywhere not just promoter. GCR can form heterodimers with other TF like fos and jun which activate transcription via AP-1 cis elements. Other complexes can repress the action of GCR at GRE.

20. Agreement between mRNA and protein

21. Where does translation take place
Where does translation take place? On ribosomes, in cell bodies, ALSO in dendrites. RNA binding proteins like BRCA-1 target RNAs to active synapses where they await translation upon stimulation. Ion channels, kinases, phosphatases, etc.