Seminar Syllabus for Biology 164: Genetic Regulation in Eukaryotes, 2005. Refer to laboratory section of web pages for laboratory schedule:
http://pages.pomona.edu/~llh04747/genreg.html
WEEK 1: Tues, August
30. Organization
and background discussion on transcriptional regulation and
post-transcriptional stability of mRNA.
Sign up to lead discussions for session in second week and first session in
third week.
Thurs Sept 1, Lecture/Discussion. Eukaryotic regulation overview; evidence that messenger RNA rather than DNA provides the basis for tissue specific regulation. Optional reading in background text Genes VII, pp 80-81(gene expression), chapter 5 (mRNA), 234-240 transcription). Differences between prokaryotic and eukaryotic regulation. K Struhl, Fundamentally different logic of gene regulation in eukaryotes and prokaryotes. Cell 98:1-4 (1999).
WEEK 2: Tues Sept 6 Topic: Gene Expression by Transcription. Skim Latchman section 1 and 2 (up to p 60). Also read for background: Gerhold et al., DNA chips: promising toys have become powerful tools, Trends in Biochemical Sciences 24:168-173. Read carefully for discussion: White et al., Microarray analysis of Drosophila development during metamorphosis. Science 286:2179-2184 (1999). Bring to class a paragraph summarizing White et al.'s findings about particular groups of genes and giving examples of the genes in each group. Discussion leader: Patrick Mitchell
Thurs, September 8
Topic: Post-transcriptional gene expression regulation. First examples are alternative splicing of
precursor RNAs and transport of mRNA to tissue of expression. Read
section 3 in Latchman. Read carefully for discussion Crenshaw,
p71, on neuron-specificity in RNA processing. Bring to class a paragraph summarizing the evidence used by these
authors and how it supports their hypothesis. Also read carefully for discussion Huang, T, Bohlenius,
H, Eriksson, S, Parcy, F, and Nilsson, O, The mRNA of the Arabidopsis
gene FT moves from leaf to shoot apex and induces flowering.
Scienceexpress 11 Aug, 2005, available through the library PubMed account in
advance of publication in Science.
Sign up to lead discussions for rest of semester.
Discussion leader: JP Wright
WEEK 3, Tues,
Sept 13, Discussion. Continued discussion of post transcriptional
regulation of gene expression. Example of translation product controlling mRNA
stability. Reread the commentary on section 4 in Latchman and read
carefully for discussion Yen et al., p93, on the stability of tubulin
mRNA. Bring a paragraph summarizing the difference between the
mechanism described in this paper and that in the Casey et al. paper (which was
not discussed in class). Discussion
leader: Patrick Mitchell Begin to define a paper topic and prepare to
hand in materials due next week by choosing a research paper (not a review
article) you would read for that topic. Suggested topics, ideas,
etc for your 10 page term paper are given at a clickable site under the course
web page.
Thurs, Sept 16, Discussion. Continued post-transcriptional regulation. RNAi inhibition of mRNA usage. Read for background, this brief review: B.R.G.Williams, Dicing with siRNA, Nature Biotechnology 23:181-2(2005). Read carefully for discussion these papers: Knight and Bass, A role for the RNAse III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science 293:2269-2271 (2001) and Ketting, R et al, Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 15: 2654-2659 (2001) Discussion leader: Jon Lee
WEEK 4: Tues, Sept 20, Topic retrospective: gene expression by transcription and post-transcriptional regulation, group discussion leader LH. Bring to class a paragraph answering these questions: For these two topics, what's the state of our understanding of the field as shown in the readings? What areas are still unknown or unclear? What kinds of experiments would be good to do now? DUE: PAPER TOPIC AND ALL BIBLIOGRAPHIC DETAILS (authors, complete title, journal, volume, pages, year) ON ONE ARTICLE FOR YOUR PAPER (Please do not choose a review article; you may use and cite review articles when writing the paper itself, but the five articles on which the paper is based may NOT include any review articles). Also, Lecture/Discussion on new topic: Chromatin structure and epigenetic regulation. Optional Genes VII reading: Chapter 19 (nucleosomes and packing of chromatin. LH.
Thurs, Sept 22, Discussion. Chromatin structure and epigenetic
regulation; chromatin remodeling. Read commentary on section 5 and review
article by Berger and Felsenfeld,
Chromatin goes global, Molecular Cell 8:263-8 (2001).
Read and prepare to discuss: Kwon et al., Nucleosome disruption and
enhancement of activator binding by a human SWI/SNF complex. Nature
370:477-481 (1994) and Bochar et al., BRCA1 is associated with a human
SWI/SNF-related complex: linking chromatin remodeling to breast cancer. Cell
102:257-265 (2000).
Discussion leader: JP Wright
WEEK 5: Tues, Sept 27,
Discussion. Chromatin
structure and epigenetic regulation, nuclear matrix interactions. Read
carefully for discussion Cai, S, Han, H-J, and Kohwi-Shigematsu,
T. Tissue-specific nuclear architecture and gene expression regulated by
SATB1. Nature Genetics 34:42-51 (2003).
Discussion leader: Jon Lee
Thurs, Sept 29,
Discussion. Chromatin;
DNA methylation. Reread commentary on section 5 and read the review
article by Rhazin, CpG methylation, chromatin structure and gene
silencing--- a three-way connection. EMBO Journal 17:4905-4908 (1998) for
background. Read for discussion: McGhee and Ginder, p 125 in
Latchman, on the role of DNA methylation in regulation of chicken hemoglobin
gene expression and Zhang, Q., Wang, H, Marzer, M, Raghunath,PN,
Nagasawa, T and Waski, M. STAT3-and DNA methyltransferase 1-mediated
epigenetic silencing of SHP-1 tyrosine phosphatase tumor suppressor gene in
malignant T lymphocytes. Proc Natl Acad Sci
WEEK 6: Tues, Oct 4,
Discussion. Chromatin,
imprinting. Read for
background Allshire and Bickmore, Pausing for thought on the boundaries
of imprinting. Cell 102:705-708 (2000.) Read carefully for discussion the article by Khosla
et al, Parental allele-specific configuration in a boundary-imprinting-control
element upstream of the mouse H19 gene. Molec and Cell Biol 19:2556-2566
(1999). Also read Bourc'his et al., Dnmt3L and the establishment
of maternal genomic imprints. Science 294:2536-2539 (2001).
Discussion leader:
Thurs, Oct 6, Discussion. Chromatin; X-inactivation. Read
for introduction: Heard, E. Recent advances in X-chromosome
inactivation. Current Opinion in Cell Biology 16:247-255 (2004). Read for
discussion: Hernandez-Munoz,
WEEK 7: Tues, Oct 11,
Discussion. Chromatin:
Histone acetylation and methylation. Reread Struhl for
background. Read carefully for discussion Kuo et al, Genes Dev.
12:627-639 (1999), on action of the Gcn5 histone acetylase near an active
promoter, Litt et al.,
Correlation between histone lysine methylation and developmental changes at the
chicken b-globin locus.
Science 293:2453-2455 (2001), and Pal-Bhadra, M., et al.,
Heterochromatic silencing and HP1 localization in Drosophila are
dependent on the RNAi machinery, Science 202:669-672 (2004).
Discussion leader:
Thurs, Oct 13, Topic retrospective: chromatin and epigenetic regulation, Bring to class a paragraph answering these questions: For this topics, what's the state of our understanding of the field as shown in the readings? What areas are still unknown or unclear? What kinds of experiments would be good to do now? Group discussion leader: LH. Also, Short Lecture/discussion on new topic: DNA Binding Sites for Regulatory Proteins: Promoters and enhancers. Optional reading in Genes VII p618-640 (Initiation of transcription; promoters and enhancers). LH.
WEEK 8: Tues, Oct 18, Fall Break, no class.
Thurs, Oct 20, Discussion. DNA Binding
Sites: Promoters and Enhancers. Read Latchman commentary 7; read carefully for discussion Banerji
et al., p 161, on an enhancer that regulates expression of antibody genes and
an early paper on the ChIP on Chip technique: Iyer et al, Genomic
binding sites of the yeast cell-cycle transcription factors SBF and MBF.
Nature 409:533-538 (2001); see: http://genome-www.stanford.edu/chromatinip/sbfmdf.pdf .
Discussion leader:
WEEK 9: Tues, Oct 25.
Discussion, DNA binding sites. Review Latchman commentary 7. Read carefully for discussion
the Hanahan paper, p 173, on pancreatic tumorigenesis in transgenic mice
caused by an enhancer being attached to an oncogene.
Discussion leader:
Thurs, Oct 27. Lecture/Discussion RNA Polymerase II; general and specific transcription factors. Optional reading in Genes VII pp641-646. Read as background Cramer et al., Structural basis of transcription: RNA polymerase II at 2.8 Angstrom resolution. Science 292:1863-1882 (2001).
Thurs, Oct 28, WEEK 10. Tues, Nov 1. Discussion. For background, carefully read the Latchman commentary on section 8. Read carefully for presentation both the Kadonaga and Tjian paper, p 195, on the first purification of a transcription factor, and the paper by Kadonaga et al., p 201, on the functional analysis of the Sp1 transcription factor. Discussion leader:
Thurs, Nov 3. Dr Hoopes may be in
WEEK 10. Tues, Nov 8. Discussion, Transcription factors. Skim the article by Kissinger et al, p 223, on the crystal structure of the complex of the engrailed protein homeodomain and the DNA to which it binds. Read carefully for discussion Passner et al. Structure of a DNA-bound Ultrabithorax-Extradenticle homeodomain complex. Nature 397:714-719, (1999). Discussion Leader:
Thurs, Nov 10. Discussion, Transcription factors. Read the commentary for
section 10 in Latchman. Read carefully for discussion Landschutz
et al, p 237, on dimerization via the leucine zipper structure and Gonzalez
and Montminy, Latchman p 257, on control of the CREB transcription factor
via phosphorylation controlled by cAMP levels . Discussion
leader:
NOTE: Paper is due next Tuesday, the Tuesday
before Thanksgiving!! Paper
is to be about 10 pp of text, with copied figures added as needed to make the
discussion clear to the reader. Paper is to be an in depth analysis
of 5 related papers (one of which was reviewed and approved when you
submitted it Sept 21) from the recent literature on an approved topic.
The paper introduction should highlight the relationship of the area chosen to
other topics covered in the course, the main body should examine the logic of
the experiments done by each team and the support they provide for the
hypotheses (very similar to class discussions we have had), and in conclusion,
should discuss the relationship between the findings in the various
papers. The best papers will give approximately equal treatment to each of
the 5 main articles on which the analysis is based. If appropriate,
your conclusion should include your model of how the regulatory system under
study appear to work. Complete and accurate bibliographic information
should be presented in the style used by the journal Molecular and Cellular
Biology.
WEEK 11, Tues, Nov 15.
Discussion, Transcription factors. Read the commentary to section 12 in Latchman and read
carefully for discussion Kaffman et al., The receptor Msn5
exports the phosphorylated transcription factor Pho4 out of the nucleus.
Nature 396:482-486 (1998) and Mitsui, K, Tokuzawa, Y, Itoh, H,
Segawa, K, Murakami, M, Takhashi, K, Maruyama, M, Maeda, M, and Yamanaka,
S. The homeoprotein Nanog is required for maintenance of pluripotency in
mouse epiblast and ES cells. Cell 113:631-642 (2003). . Discussion leader:
Thursday, Nov 17, Discussion, Transcription factor regulation. Read for discussion Martinez-Garcia et al., Direct targeting of light signals to a promoter element-bound transcription factor. Science 288:859-891 (2000). Discussion leader:
WEEK 12, Tuesday, Nov 22: PAPER IS DUE IN CLASS TODAY!! Paper is to be about 10 pp of text, with copied figures added as needed to make the discussion clear to the reader. Paper is to be an in depth analysis of 5 related papers from the recent literature on an approved topic. The paper should highlight the relationship of the area chosen to other topics covered in the course, should examine the logic of the experiments done by each team and the support they provide for the hypotheses, and should discuss the relationship between the findings in the various papers. If appropriate, you should include your model of how the regulatory system under study appear to work. Complete and accurate bibliographic information should be presented in the style used by the journal Molecular and Cellular Biology. Discussion, Transcription factors. Reread Latchman's commentary to sections 12 and 13, and read for discussion Baurle and Baltimore, p 263, on a specific inhibitor of the transcription factor NF-KB that regulates expression of antibody genes and Henry and Melton, Mixer, a homeobox gene required for endoderm development, Science 281:91-96 (1998). Discussion leader:Laura Hoopes
Thursday, November 24, Thanskgiving, no class! Enjoy
feasting and resting!
WEEK 13, Tuesday, Nov 29, Discussion, transcription factors, cont. Read carefully for discussion, Glannakou, M, Goss, M, Junger, M, Hafen, E, Leevers, S, and Partridge, L Long-lived Drosophila with overexpressed dFOXO in adult fat body. Science 305:361 (2004) and Hwangbo DS, Gershman B, Tu MP, Palmer M, Tatar M, Drosophila dFOXO controls lifespan and regulates insulin signaling in brain and fat body. Nature 429:562-6 (2004).
Thursday, December 1,
Retrospective on RNA Polymerase II (mRNA), transcriptional Regulation via
promoters/enhancers, and transcription factors, group discussion leader LH.
Bring to class a paragraph answering these questions: For this topic group,
what's the state of our understanding of the field as shown in the
readings? What areas are still unknown or unclear? What kinds of
experiments would be good to do now? Also: planning for class
discussion of the contenders for aesthetic paper of the year.
Week 14: Tuesday, December 6, last day of class, Discussion. MANDATORY CLASS!! If you must miss this class, you must make prior arrangements with Dr. Hoopes. Retrospective overall discussion of the class, examining the approaches used, the overall picture of eukaryotic regulation developed, and the excellence of the papers reviewed (personal aesthetic appreciation required!).