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7.342: Reading the Blueprint of Life: Transcription, Stem Cells, & Differentiation

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Week 1: Introduction

Course Syllabus


Week 2: Chromatin Functions to Define Cell State


Chromosomal Subunits in Active Genes Have an Altered Conformation

Weintraub, H & Groudine, M. (1976) Science 193, 848-856.

Hyperdynamic Plasticity of Chromatin Proteins in Pluripotent Embryonic Stem Cells

Meshorer, E, Yellajoshula, D, George, E, Scambler, PJ, Brown, DT, & Misteli, T. (2006) Dev Cell 10, 105-116.

Bonus Materials

Commentary on Meshorer et al paper

Supplemental Data for Meshorer et al paper

Obituary for Harold Weintraub from Molecular Biology of the Cell, 1995 (by Marc Kirschner)

Obituary for Harold Weintraub from Cell, 1995 (by Richard Axel & Tom Maniatis)

Week 3: Chromatin Structure and Discovery of Chromatin Modifying Enzymes


Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation.

Brownell, J. E., Zhou, J., Ranalli, T., Kobayashi, R., Edmondson, D. G., Roth, S. Y., and Allis, C. D. (1996). Cell 84, 843-851.

A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p.

Taunton, J., Hassig, C. A., and Schreiber, S. L. (1996). Science 272, 408-411.

Bonus Materials

Commentary on HAT Discovery

Review on HDACs and Cancer

Obituary of Alan Wolffe: Champion of Chromatin

Profile of C. David Allis

Week 4: Methylation and the Emergence of the "Histone Code"


Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins.

Lachner, M., O'Carroll, D., Rea, S., Mechtler, K., and Jenuwein, T. (2001). Nature 410, 116-120.

WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development.

Wysocka, J., Swigut, T., Milne, T. A., Dou, Y., Zhang, X., Burlingame, A. L., Roeder, R. G., Brivanlou, A. H., and Allis, C. D. (2005). Cell 121, 859-872.

Bonus Materials

Translating the Histone Code

Histone Code and Chromatin Cross-Talk

Week 5: Heritable Gene Expression


Rb targets histone H3 methylation and HP1 to promoters.

Nielsen, S. J., Schneider, R., Bauer, U. M., Bannister, A. J., Morrison, A., O'Carroll, D., Firestein, R., Cleary, M., Jenuwein, T., Herrera, R. E., and Kouzarides, T. (2001). Nature 412, 561-565

Regulated recruitment of HP1 to a euchromatic gene induces mitotically heritable, epigenetic gene silencing: a mammalian cell culture model of gene variegation.

Ayyanathan, K., Lechner, M. S., Bell, P., Maul, G. G., Schultz, D. C., Yamada, Y., Tanaka, K., Torigoe, K., and Rauscher, F. J., 3rd (2003). Genes Dev 17, 1855-1869.

Bonus Materials

Commentary on the Human Epigenome Project

Epigenetics and Cancer Review

Week 6: Pluripotency Regulators & Stem Cell Differentiation


Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells.

Chambers, I, Colby, D, Robertson, M, Nichols, J, Lee, S, Tweedle, S, & Smith, A. (2003). Cell 113, 643-655.

Directed differentiation of embryonic stem cells into motor neurons.

Wichterle, H, Lieberam, I, Porter, JA, & Jessell, TM. (2002). Cell 110, 385-397.

Bonus Materials

Commentary on Chambers et al paper

Perspective on potential uses for ES cells and issues they raise

Recent review on the current state of understanding of the molecular factors which contribute to pluripotency

NIH report on prospects for neural regeneration using stem cells

Article from the San Francisco Chronicle about when human trials of stem cell therapies for neurodegenerative disorders might happen