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Understanding epigenetic regulation: Tracking protein levels across multiple generations of cells

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Abstract

Cells and organisms are remarkably robust: they alter the variety and levels of expressed genes and proteins in response to environmental stimuli, including temperature, chemicals, and the stiffness of their surroundings. Ultimately changes in gene and protein expression can result in a distinct phenotypic state, which in some cases is maintained over multiple generations; the ability to pass on a particular phenotypic state to progeny cells is critical for differentiation. Moreover, epigenetic regulation of phenotype is also thought to provide an evolutionary advantage for a population of cells adapting to a fluctuating environment on faster timescales than the occurrence of genetic mutations. However, simple methods to study patterns of gene and protein expression on multi-generational timescales are sparse. Here we describe a technique to study lineages of single cells over multiple generations using a microfluidic device; this reveals patterns of expression where protein levels are correlated across multiple generations. Such quantitative information of protein expression in the context of pedigree remains hidden when studying the population as an ensemble.

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References

  • M.B. Elowitz, A.J. Levine, E.D. Siggia, P.S. Swain, Science 297, 1183 (2002)

    Google Scholar 

  • A. Raj, C.S. Peskin, D. Tranchina, D.Y. Vargas, Tyagi S., PLoS Biol. 4, e309 (2006)

  • Raj A., van Oudenaarden A., Cell 135, 216 (2008)

    Google Scholar 

  • Raser J.M., O'Shea E.K., Science 304, 1811 (2004)

  • Raser J.M., O'Shea E.K., Science 309, 2010 (2005)

  • Cai L., Friedman N., Xie X.S., Nature 440, 358 (2006)

    Google Scholar 

  • Kasza K.E., Rowat A.C., Liu J., Angelini T.E., Brangwynne C.P., Koenderink G.H., Weitz D.A., Curr. Opin Cell. Biol. 19, 101 (2007)

    Google Scholar 

  • Gasch A.P., Spellman P.T., Kao C.M., Carmel-Harel O., Eisen M.B., Storz G., Botstein D., Brown P.O., Mol. Biol. Cell. 11, 4241 (2000)

    Google Scholar 

  • Meshorer E., Misteli T., Nat. Rev. Mol. Cell. Biol. 7, 540 (2006)

    Google Scholar 

  • Vermaak D., Ahmad K., Henikoff S., Curr. Opin. Cell. Biol. 15, 266 (2003)

    Google Scholar 

  • Felsenfeld G., Groudine M., Nature 421, 448 (2003)

  • Jablonka E., Lamb M.J., Evolution in Four Dimensions: Genetic, Epigenetic, Behavioral, and Symbolic Variation in the History of Life (MIT Press, Cambridge, USA, 2005)

  • Rando O.J., Verstrepen K.J., Cell 128, 655 (2007)

    Google Scholar 

  • Lachmann M., Jablonka E., J. Theor. Biol. 181, 1 (1996)

    Google Scholar 

  • Lang G.I., Murray A.W., Genetics 178, 67 (2008)

  • Li L., Lindquist S., Science 287, 661 (2000)

    Google Scholar 

  • Smith C.M., Haimberger Z.W., Johnson C.O., Wolf A.J., Gafken P.R., Zhang Z.Parthun M.R.Gottschling D.E., Proc. Natl. Acad. Sci. USA 99, 16454 (2002)

    Google Scholar 

  • Huh W.K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S.O'Shea E.K., Nature 425, 686 (2003)

    Google Scholar 

  • Newman J.R., Ghaemmaghami S., Ihmels J., Breslow D.K., Noble M., DeRisi J.L., Weissman J.S., Nature441, 840 (2006)

    Google Scholar 

  • Bar-Even A., Paulsson J., Maheshri N., Carmi M., O'Shea E., Pilpel Y., Barkai N., Nat. Genet. 38, 636 (2006)

    Google Scholar 

  • Balaban N.Q., Merrin J., Chait R., Kowalik L., Leibler S., Science 305, 1622 (2004)

    Google Scholar 

  • Groisman A., Lobo C., Cho H., Campbell J.K., Dufour Y.S., Stevens A.M., Levchenko A., Nat. Meth. 2, 685 (2005)

  • Cookson S., Ostroff N., Pang, W.L.Volfson D., J. Hasty, Mol. Syst. Biol. 1, 0024 (2005)

    Google Scholar 

  • Balagadde F.K., You L., Hansen C.L., Arnold F.H., Quake S.R., Science 309, 137 (2005) 0024 (2005)

    Google Scholar 

  • Paliwal S., Iglesias P.A., Campbell K., Hilioti Z., Groisman A., Levchenko A., Nature 446, 46 (2007)

    Google Scholar 

  • Lee P.J., Helman N.C., Lim W.A., Hung P.J., Biotechniques 44, 91 (2008)

    Google Scholar 

  • Charvin G., Cross F.R., Siggia E.D., PLoS ONE 3, e1468 (2008)

  • Sia S.K., Whitesides G.M., Electrophoresis 24, 3563 (2003)

  • Yen R.T., Fung Y.C., Am. J. Physiol. 235, H251 (1978)

  • Rowat A.C., Bird J., Agresti J.J., Rando O.J., Weitz D.A., Proc. Natl. Acad. Sci. USA 106, 18149 (2009)

    Google Scholar 

  • Wykoff D.D., Rizvi A.H., Raser J.M., Margolin B., O'Shea E.K., Mol. Cell. 27, 1005 (2007)

    Google Scholar 

  • Brandman O., Meyer T., Science 322, 390 (2008)

    Google Scholar 

  • Ferrell J.E. Jr., Curr. Opin. Cell. Biol. 14, 140 (2002)

    Google Scholar 

  • Novick A., Weiner M., Proc. Natl. Acad. Sci. 43, 553 (1957)

    Google Scholar 

  • Ghaemmaghami S., Huh W.K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S., Nature 425, 737 (2003)

    Google Scholar 

  • Friedman N., Cai L., Xie X.S., Phys. Rev. Lett. 97, 168302 (2006)

    Google Scholar 

  • Newlands S., Levitt L.K., Robinson C.S., Karpf A.B., Hodgson V.R., Wade R.P., Hardeman E.C., Genes Dev. 12, 2748 (1998)

  • Zenklusen D., Larson D.R., Singer R.H., Nat. Struct. Mol. Biol. 15, 1263 (2008)

    Google Scholar 

  • Chubb J.R., Trcek T., Shenoy S.M., Singer R.H., Curr. Biol. 16, 1018 (2006)

    Google Scholar 

  • Lahav G., Rosenfeld N., Sigal A., Geva-Zatorsky N., Levine A.J., Elowitz M.B., Alon U., Nat. Genet. 36, 147 (2004)

    Google Scholar 

  • Shalem O., Dahan O., Levo M., Martinez M.R., Furman I., Segal E., Pilpel Y., Mol. Syst. Biol. 4, 1 (2008)

    Google Scholar 

  • Blake W.J., Cantor K.A.M.C.R., Collins J.J., Nature 422, 633 (2003)

  • Stewart J.J., Stargell L.A., J. Biol. Chem. 276, 30078 (2001)

    Google Scholar 

  • Tirosh I., Weinberger A., Carmi M., Barkai N., Nat. Genet. 38, 830 (2006)

    Google Scholar 

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Correspondence to A. C. Rowat.

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Rowat, A., Weitz, D. Understanding epigenetic regulation: Tracking protein levels across multiple generations of cells. Eur. Phys. J. Spec. Top. 178, 71–80 (2009). https://doi.org/10.1140/epjst/e2010-01183-5

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