Epigenetic Mechanisms

Lars Jansen

The genome is propagated through cell division by duplication of a full set of chromosomes followed by the faithful separation of each chromosome copy into two new daughter cells during mitosis. In addition, so-called “epigenetic” chromosome structures that maintain functional chromosomes and that “memorize” the transcriptional state of a cell lineage are also maintained through mitotic and sometimes even meiotic divisions.

Although the mechanism of DNA inheritance has been worked out decades ago, how the more fluid epigenetic information is maintained in time is not understood. In our lab, www.jansenlab.org we focus on chromatin, the protein DNA complex that packages DNA. We ask whether histone proteins, which make up the nucleosome, can carry “memory” of gene expression or chromatin structure.

Researchers approach the problem by:

1) taking aim at the human centromere, a locus connecting chromosomes to the mitotic spindle during mitosis. This chromatin domain is a paradigm for epigenetic inheritance as it is defined by unique self-templating chromatin proteins.

Further,

2) focus on long-term transcriptional memory in human cells to define the role of chromatin in epigenetic maintenance of gene expression.

Finally,

3)with the aim to discover the role of heritable gene expression on evolutionary adaption in yeast populations. Note that while me maintain an affiliation with the IGC, our lab is located at the University of Oxford, Department of Biochemistry. If you are interested in our lab please see our lab page at www.jansenlab.org or at www.bioch.ox.ac.uk/research/jansen

Publications

Stankovic, A., Guo, L.Y., Mata, J.F., Bodor, D.L., Cao, X-J., Bailey, A.O., Shabanowitz, J., Hunt, D.F., Garcia, B.A., Black, B.E., Jansen, L.E.T. (2017) A dual inhibitory mechanism sufficient to maintain cell cycle restricted CENP-A assemblyMol Cell. 65 : 231–246
Deaton, A.M., Gomez-Rodriguez, M., Mieczkowski, J., Tolstorukov, M.Y., Kundu, S., Sadreyev, R.I., Jansen, L.E.T., Kingston, R.E. (2016) Enhancer regions show high histone H3.3 turnover that changes during differentiation. eLife 5 : e15316

Falk, S.J., Guo, L.Y., Sekulic, N., Smoak, E.M., Mani, T., Logsdon, G.A., Gupta, K., Jansen, L.E.T., Van Duyne, G.D., Vinogradov, S.A., Lampson, M.A., Black, B.E. (2015) CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere.Science 348 : 699-703
Bodor, D.L., Mata, J.F., Sergeev, M., David, A.F., Salimian, K.J., Panchenko, T., Cleveland, D.W., Black, B.E., Shah, J.V., Jansen, L.E.T. (2014) The quantitative architecture of centromeric chromatin eLife 3 : e02137
Bodor, D.L., Valente, L.P., Mata, J.F., Black, B.E., Jansen, L.E.T. (2013) Assembly in G1 phase and Long-Term Stability are Unique Intrinsic Features of CENP-A nucleosomes Mol Biol Cell. 24 : 923-932  
Silva, M.C.C., Bodor, D.L., Stellfox, M.E., Martins, N.M., Hochegger, H., Foltz, D.R., Jansen, L.E.T. (2012) Cdk activity couples epigenetic centromere inheritance to cell cycle progression Dev Cell. 22(1) : 52-63
Jansen, L.E.T. (2012) Sowing the seeds of centromeres Science 335(6066) : 299-300
Bergmann, J.H., Gómez-Rodríguez, M., Martins, N.M.C., Kimura, H., Kelly, D.A., Masumoto, H., Larionov, V., Jansen, L.E.T., Earnshaw, W.C. (2011) Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore EMBO J. 30 : 328-40
Gallet, D. R., Woolfe, A., Vassias, I., Pellentz, C., Lacoste, N., Puri, A., Schultz, D.C., Pchelintsev, N.A., Adams, P.D., Jansen, L.E.T., Almouzni, G. (2011) Dynamics of histone H3 deposition in vivo reveal a gap filling mechanism for H3.3 to maintain chromatin integrity Mol Cell. 44 : 928-41
Carroll, C.W., Silva, M.C.C., Godek, K.M., Jansen, L.E.T., Straight, A.F. (2009) Centromere assembly requires the direct recognition of CENP-A nucleosomes by CENP-N Nat Cell Biol 11 : 896-902