BGS Home » Current Students » Academics » Course Information » Fall 2007 Course List » CAMB 608 Regulation of Eucaryotic Gene Transcription

CAMB 608 Regulation of Eucaryotic Gene Transcription

MOLECULAR BIOLOGY 608 -- FALL 2007

REGULATION OF EUCARYOTIC GENE TRANSCRIPTION

Dr. Tom Kadesch (898-1047; kadesch@mail.med.upenn.edu)

            This is course intended to bring students up to date concerning our understanding of transcriptional regulation in eukaryotes.  It will be based on assigned readings, formal presentations by individual class members, and the critical evaluation of primary data.  Each student will be responsible for one topic.  Each of these will focus on two to three papers and, together, will cover a variety of experimental systems and concepts. 

            Individual presentations should be organized as seminars, and include approximately 10-20 minutes of introduction that will supply background information about the experimental system and its significance.  The introductory material should be derived from extensive additional reading, not just the assigned papers and reviews.  After the introduction, the presentation will be devoted to a critical evaluation of the experiments and conclusions of the assigned papers.  Students should not give simply a blow-by-blow account of each experiment and the authors’ conclusions.  The papers should be presented more as if they were the students' own work — it is possible that some figures will not be discussed.  The topics build on one another, so as the course proceeds students should be able to relate and compare the data and conclusions of the papers being discussed to those of previous discussions, pointing out apparent consistencies and differences.

            On the Thursday or Friday before their talks, presenters should provide an outline and discuss their presentations with Dr. Kadesch.  Call or email to make an appointment.

            The papers will also be critically evaluated by each class member.  Lively discussion and criticism involving all members of the class is expected.  The papers should be treated as if they were being reviewed for publication in a journal (despite the fact that they’re already published!), and students should be prepared to discuss both a paper’s strengths and weaknesses.  A high level of discussion will not occur unless each participant thoroughly reads the papers and formulates questions.  Accordingly, each student will be required to prepare one question from each of the assigned papers prior to class.  The questions should be well formulated, possibly citing specific data (e.g. lanes in gels) or quotations from the text.  Although it would not be unreasonable for the length of a well-designed question to approach 1/2 type-written page, they should be expressed succinctly.  Each week's questions must be written out and handed in at the beginning of class.

            Grades will be based on students' presentations as well as weekly participation in the discussions and submitted questions.  Dr. Kadesch will provide an evaluation of each student’s performance within a week of the presentation (call to set up a time).  Evaluations of each presentation will also be provided by the class using standard forms.  These will be given directly to the presenter at the end of class for his/her own use; they will not be read by Drs. Kadesch or Zaret.  This peer review will allow the presenters to obtain more input concerning their presentations.  This should help in the preparation of future scientific talks such as thesis committee meetings, thesis defenses, and eventually job seminars.

1.         BASAL MACHINERY

A.   Black, J.C., Choi, J.E., Lombardo, S.R., Carey, M. (2006). A Mechanism for Coordinating Chromatin Modification and Preinitiation Complex Assembly. Molecular Cell 23: 809-818.

B.   Marr, M.T, II, Isogai, Y., Wright, K.J., Tjian, R. (2006).  Coactivator cross-talk specifies transcriptional output.  Genes & Dev. 20: 1458-1469.

C.  Yang, F., Vought, B.W., Satterlee, J.S., Walker, A.K., Jim Sun, Z.-Y., Watts, J.L., DeBeaumont, R., Saito, R.M., Hyberts, S.G., Yang, S., Macol, C., Iyer, L., Tjian, R., van den Heuvel, S., Hart, A.C., Wagner, G., Naar, A.M. (2006). An ARC/Mediator subunit for SREBP control of cholesterol and lipid homeostasis. Nature 442: Letters.

2.         HISTONE DYNAMICS:  NUCLEOSOME DISPLACEMENT

A.   Boeger, H., Griesenbeck, J., Strattan, J.S., Kornberg, R.D. (2003). Nucleosomes Unfold Completely at a Transcriptionally Active Promoter. Molecular Cell 11: 1587-1598.

B.  Boeger, H., Griesenbeck, J., Strattan, J.S., Kornberg, R.D. (2004).  Removal of Promoter Nucleosomes by Disassembly Rather Than by Sliding In Vivo.  Molecular Cell 14: 667-673.

C. Adkins M.W., Tyler, J.K. (2006). Transcriptional Activators Are Dispensable for Transcription in the Absence of Spt6-Mediated Chromatin Reassembly of Promoter Regions. Molecular Cell 21: 405–416.

3.         HISTONE DYNAMICS:  METHYLATION

  1. Yamane, K., Toumazou, C., Tsukada, Y., Erdjument-Bromage, H., Tempst, P., Wong, J., Zhang, Y. (2006).  JHDM2A, a JmjC-Containing H3K9 Demethylase, Facilitates Transcription Activation by Androgen Receptor. Cell 125: 483–495.

B.    Garcia-Bassets, I., Kwon, Y.S., Telese, F., Prefontaine, G.G., Hutt, K.R., Cheng, C.S., Ju, B.G., Ohgi, K.A., Wang, J., Escoubet-Lozach, L., Rose, D.W., Glass, C.K., Fu, X.D., Rosenfeld, M.G. (2007). Histone Methylation-Dependent Mechanisms Impose Ligand Dependency for Gene Activation by Nuclear Receptors. Cell 128: 505-518.

4.         GLOBAL REGULATION:  POLYCOMB

A.   Bracken, A.P., Dietrich, N., Pasini, D., Hansen, K.H., Helin, K. (2006). Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes & Dev. 20: 1123-1136.

B.   Agger, K., Cloos, P.A.K., Christensen, J., Pasini, D., Rose, S., Rappsilber, J., Issaeva, I., Canaani, E., Salcini, A.E., Helin, K. (2007). UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature: Letters.

C.  Rinn, J.L., Kertesz, M., Wang, J.K., Squazzo, S.L., Xu, X., Brugmann, S.A., Goodnough, L.H., Helms, J.A., Farnham, P.J., Segal, E., Chang, H.Y. (2007). Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNA’s. Cell 129: 1311-1323.

5.         GLOBAL REGULATION:  DNA METHYLATION

A.   Smallwood, A., Esteve, P.O., Pradhan, S. Carey, M. (2007). Functional cooperation between HP1 and DNMT1 mediates gene silencing. Genes & Development 21: 1169-1178.

  1. Ooi, S.K.T., Qiu, C., Bernstein, E., Li, K., Jia, D., Yang, Z., Bromage-Erdjument, H., Tempst, P., Lin, S.P., Allis, C.D., Cheng, X., Bestor, T.H. (2007). DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 448: Letters.

6.         GLOBAL REGULATION:  INSULATOR/BOUNDARY ELEMENTS

A.   Yusufzai, T.M., Tagami, H., Nakatani, Y., Felsenfeld, G. (2004). CTCF Tethers an Insulator to Subnuclear Sites, Suggesting Shared Insulator Mechanisms across Species Molecular Cell: 13: 291–298.

B.   Ishihara, K., Oshimura, M., Nakao, M. (2006). CTCF-Dependent Chromatin Insulator is Linked to Epigenetic Remodeling. Molecular Cell 23: 733-742.

7.         “CLASSIC” TRANSCRIPTION FACTORS:  ESTROGEN RECEPTOR

A.   Carroll, J.S., Liu, X.S., Brodsky, A.S., Li, W., Meyer, C.A., Szary, A.J., Eeckhoute, J., Shao, W., Hestermann, E.V., Geistlinger, T.R., Fox, E.A., Silver, P.A., Brown, M. (2005).  Chromosome-Wide Mapping of Estrogen Receptor Binding Reveals Long-Range Regulation Requiring the Forkhead Protein FoxA1. Cell 122: 33–43.

B.   Cheng, A.S.L., Jin, V.X., Fan, M., Smith, L.T., Liyanarachchi, S., Yan, P.S., Leu, Y.-W., Chan, M.W.Y., Plass, C., Nephew, K.P., Davuluri, R.V., and Huang, T.H.-M.  (2006). Combinatorial Analysis of Transcription Factor Partners Reveals Recruitment of c-MYC to Estrogen Receptor-a Responsive Promoters. Molecular Cell 21:  393–404.

8.         “CLASSIC” TRANSCRIPTION FACTORS: NF-k

A.   Lim, C.A., Yao, F., Wong, J.J.-Y., George, J., Xu, H., Chiu, K.P., Sung, W.K., Lipovich, L.,  Vega, V.B., Chen, J., Shahab, A., Zhao, X.D., Hibberd, M., Wei, C.-L., Lim, B., Ng, H.H., Ruan, Y., Chin, K.C. (2007). Genome-wide Mapping of RELA(p65) Binding Identifies E2F1 as a Transcriptional Activator Recruited by NF-kB upon TLR4 Activation. Molecular Cell 27: 622-635.

  1. Huang, W.C., Ju, T.K., Hung, M.C., Chen, C.C. (2007) Phosphorylation of CBP by IKKa Promotes Cell Growth by Switching the Binding Preference of CBP from p53 to NF-kB. Molecular Cell 26: 75-87.

9.         WNT / WINGLESS

A.   Mosimann, C., Hausmann, G., Basler, C. (2006).  Parafibromin/Hyrax activates Wnt/Wg target gene transcription by direct association with b-catenin/Armadillo. Cell 125: 327-341. 

B.   Sansom, O.J., Meniel, V.S., Muncan, V., Phesse, T.J., Wilkins, J.A., Reed, K.R., Vass, J.K., Athineos, D., Clevers, H., Clarke, A.R. (2007). Myc deletion rescues Apc deficiency in the small intestine. Nature 446: Letters.

10.       CLOCK

11.       MUSCLE

A.   Liu, Z.-P., Wang, Z., Yanagisawa, H., Olson, E.N.  (2005). Phenotypic Modulation of Smooth Muscle Cells through Interaction of Foxo4 and Myocardin. Developmental Cell 9: 261–270.

B.   Creemers, E.E., Sutherland, L.B., Oh, J., Barbosa, A.C., Olson, E.N. (2006).  Coactivation of MEF2 by the SAP Domain Proteins Myocardin and MASTR.  Molecular Cell 23: 83–96.

12.       UNFOLDED PROTEIN RESPONSE

A.   Acosta-Alvear, D., Zhou, Y., Blais, A., Tsikitis, M., Lents, N.H., Arias, C., Lennon, C.J., Kluger, Y., Dynlacht, B.D. (2007). XBP1 Controls Diverse Cell Type- and Condition-Specific Transcriptional Regulatory Networks. Molecular Cell 27: 53-66.

B.   Zhang, K., Shen, X., Wu, J., Sakaki, K., Saunders, T., Rutkowski, D.T., Back, S.H., Kaufman, R.J. (2002) Endoplasmic Reticulum Stress Activates Cleavage of CREBH to Induce a Systemic Inflammatory Response. Cell 124: 587–599.

13.       NOTCH / KERATINOCYTES

  1. Mammucari, C., Tommasi di Vignano, A., Sharov, A.A., Neilson, J., Havrda, M.C., Roop, D.R., Botchkarev, V.A., Crabtree, G.R., Dotto, G.P. (2005).  Integration of Notch 1 and Calcineurin/NFAT Signaling Pathways in Keratinocyte Growth and Differentiation Control. Developmental. Cell 8: 665–676.

14.       GLOBAL ANALYSIS OF THE “HISTONE CODE”

A.   Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, and Zhao K. (2007). High-resolution profiling of histone methylations in the human genome.

      Cell 129: 823-837.

B.   Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP, Lee W, Mendenhall E, O'Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander ES, and Bernstein BE.  (2007). Genome-wide maps of chromatin state in pluripotent and lineage-committed cells.  Nature 448: 553-560.

C.  Guenther MG, Levine SS, Boyer LA, Jaenisch R, and Young RA (2007).  A chromatin landmark and transcription initiation at most promoters in human cells.  Cell 130: 77-88.