Biochemistry Online: An Approach Based on Chemical Logic

Biochemistry Online




Last Updated: 03/30/16

Learning Goals/Objectives for Chapter 5D:  After class and this reading, students will be able to

  • describe general mechanisms of how a gene for a given protein might be negatively and positively regulated at the level of gene transcription;
  • describe the structure/function/role of promoters, response elements, RNA polymerase, transcription factors, nucleosomes, histone proteins, epigenetic modifications of DNA in gene transcription;
  • explain the differences (structural, Kds) between specific and nonspecific binding of a ligand to a macromolecule, at the structural level;
  • describe the structural features of both proteins and DNA that result in specific and nonspecific binding;
  • describe and give examples of how post-translational modifications of proteins and epigenetic modifications of DNA can alter gene expression;
  • explain how the apparent Kd for a protein binding to DNA can be altered by the presence of another protein bound to DNA at a proximal site
  • describe the basis of RNA interference in gene expression

D18. Links and References

  1. Amy R. Strom et al. Phase separation drives heterochromatin domain formation. doi:10.1038/nature22989 (2017)
  2. ENCODE explained. Nature 389, 52-55 (2012)
  3. The Encode Project Consortium.  An integrated encyclopedia of DNA elements in the human genome.  Nature 489, 57-74 (2012)
  4. Meijsing, S. et al.  DNA Binding Site Sequence Directs Glucorticoid Receptor Structure and Activity. Science 324, 407 (2009)
  5. Choudhary, C. et al. Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions. Science 325, 834 (2009)
  6. Redefining the p53 response element.  PNAS 106, 14373 (2009)
  7. Rhos, R. et al. The role of DNA shape in Protein-DNA recognition.  Nature 461, 1248 (2009)
  8. Geurts, A. M. et. al. Knockout Rats via Embryo Microinjection of Zinc-Finger Nucleases. Science. 325, p 433 (2009)
  9. McGowan, P. et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse.  Nature Neuroscience 12, 342 (2009)
  10. Rubartelli, A & Lotze, M. Inside, outside, upside down: damage-associated molecular pattern molecules (DAMPs) and redox.  Trends in Immunology. 28, 431 (2007) doi:10.1016/
  11. Jensen, L. and Bork, P. Not Comparable, but Complementary.  Science 322, 56 (2008)
  12. Yu, H et al. High-Quality Binary Protein Interaction Map of the Yeast Interactome Network.  Science  322, 104 (2008)
  13. Rigaut, G. et al.  A generic protein purification method for protein complex characterization and proteome exploration.  Nature Biotechnology 17, 1030 (1999)
  14. Tarassov, K. et al.     Science 320, 1465  (2008)
  15. Couzin, J. Erasing MicroRNAs Reveals Their Powerful Punch.  Science, 316, 530 (2007).
  16. Jeffery P. Demuth, Tijl De Bie, Jason E. Stajich, Nello Cristianini, Matthew W. Hahn.  The Evolution of Mammalian Gene Families
  17. Brideau, N. et al. Two Dobzhansky-Muller Genes Interact to Cause Hybrid Lethality in Drosophila.   314,1292 (2006)
  18. Segal, E. et al.  A genomic code for nucleosome positioning. Nature.  442, 772 (2006)
  19. Xiaoxia Wang et al.  PLoS Biology,  issue 3 (2006).
  20. The Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature. 437, 69 (2005); Li W. H. & Saunders, M.  The Chimpanzee and Us.  Nature 437, 50 (2005).
  21. Garza, M. and Hampton, R. Sterol Sensor comes up for air.  Nature 435, 37 (2005)
  22. Rando, O et al. Genome-Scale Identification of Nucleosome Positions in S. cerevisiae.  Science 309, 626-630, (2005)
  23. Urnov, F.D. et al. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 435, 646 (2005)
  24. The International Chimpanzee Chromosome 22 Consortium.  DNA sequence and comparative analysis of chimpanzee chromosome 22Nature 429, 382 (2004)
  25. Levine, M. & Tjian, R. Transcription regulation and animal diversity.  Nature. 424, pg 147 (2003)
  26. Kamath. R. et al. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature. 421, pg 231 (2003).
  27. Winkler. W et al. Thiamine derivative bind messenger RNAs directly to regulate bacterial gene expression.  Nature, 419, pg 852, 890 (2002)
  28. Enard et al. Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418, pg 869 (2002)
  29. Angata et al. A second uniquely human mutation affecting sialic acid biology.  J. Biol. Chem. 276, pg 40282 (2001)
  30. Dobrosotskaya et al. Regulation of SREBP Processing and Membrane Lipid Production by Phospholipids in Drosophila.  Science. 296, pg 879 (2002)
  31. Nohturfft, A. and Losick, R. Fats, Flies, and Palmitate. Science. 296, pg 857 (2002)
  32. Plasterk, R. RNA Silencing: The Genome's Immune System. Science. 296, pg 1263 (2002)
  33. Dennis, C. The Brave New World of RNA. Nature. 418, pg 122 (2002)
  34. Hannon, G. RNA Interference. Nature. 418, pg 245 (2002)
  35. Munshi et al.  Enhancers and Gene Transcription.  293, pg 1054, 1133 (2001)  
  36. Yanofsky et al. Turning Gene Regulation on its Head. (About W Operon).  Science. 293 pg 2018 (2001)
  37. Gene Expression in human and chimp brains. Science. 292, pg 44 (2001)
  38. Reprograming X Inactivation (one of two X chromosomes in female cell must be silenced) Science. 290 pg 1518 (2000)
  39. Wei et al. One Man's Food (about regulation of cyto P450) expression.  Nature. 407 pg 852, 920 (2000)
  40. Pham  and SauerNew Insight into an old modification (Tx. factor TFIID chemically modifies a histone)  Science. 289. pg 2290, 2357 (2000)
  41. Lemon et al. Specifying Transcription. Nature. 414. pg 858, 924 (2001)
  42. Nakayama et al. The Histone modification circus.  (how Histone modification regulates gene silencing)  Science.  292, pg 64 (2001)
  43. Croix et al. Genes Expressed in Human Tumor Endothelium. Science. 289, pg 1197 (2000)
  44. de Urquiza et al. Docosahexaenoic Acid, a ligand for the retinoid X receptor in mouse brain.  (ligand-activated txn factor through orphan receptor).  Science. 290. pg 2140 (2000)
  45. Jaime F. Mart�nez-Garc�a, Enamul Huq, and Peter H. Quail. Direct Targeting of Light Signals to a Promoter Element-Bound Transcription Factor. Science 288, pg 859 (2001)
  46. Nagatani, A. Lighting Up the Nucleus. Science, 288, pg 821, 2000) 
  47. A silence that speaks volumes.  (gene silencing by RNA interference) Nature, 404, pg 804 (2000)
  48. Xho et al.  How do X chromosomes set boundaries.  (Females have 2 X chromosomes, males one.  Do keep gene dosage comparable, one X chromosome must be inactivated in female clles. How is that done?  They found a protein - trans-acting factor - that key).  Science. 295. pg 287, 345 (2002)
  49. Jacobs and Khorasanizadeh. Structure of HP1 Chromodomain Bound to a Lysine 9-methylated Histone H3 tail.  Science.  295. pg 2080 (2002)


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