Department of Biochemistry University of Oxford Department of Biochemistry
University of Oxford
South Parks Road
Oxford OX1 3QU

Tel: +44 (0)1865 613200
Fax: +44 (0)1865 613201
Image showing the global movement of lipids in a model planar membrane
Matthieu Chavent, Sansom lab
Anaphase bridges in fission yeast cells
Whitby lab
Lactose permease represented using bending cylinders in Bendix software
Caroline Dahl, Sansom lab
Epithelial cells in C. elegans showing a seam cell that failed to undergo cytokinesis
Serena Ding, Woollard lab
Collage of Drosophila third instar larva optic lobe
Lu Yang, Davis lab
First year Biochemistry students at a practical class
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Lars Jansen
Mechanisms of Chromatin Inheritance

Co-workers: Bas van den Berg, João Mata, Inês Milagre, Sreyoshi Mitra, Marina Murillo, Wojtek Siwek, Sahar Tehrani

Our Central Hypothesis

An epigenetic system is composed of molecules that can survive through mitotic divisions, are self-templating in nature and their duplication and transmission is coupled to cell division.

Our Research Goals

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 is also maintained through mitotic and sometimes even meiotic divisions.

Although the mechanism of duplication and mitotic transmission of DNA sequences has been worked out decades ago, how the more fluid epigenetic information of gene activities and chromosome structure is maintained in time is not understood. We are interested in resolving this.

The Problem

We focus on chromatin, the protein DNA complex that packages DNA. Histone proteins, which make up the nucleosome may carry "memory" of gene expression or chromatin structure. To carry memory, chromatin itself need to be inherited (stable), copies (self-templated duplication) in concert with cell division (cell cycle coupling). We aim to understand all these aspects.

Publications

  1. Ana Stankovic, Lucie Y. Guo, João F. Mata, Dani L. Bodor, Xing-Jun Cao, Aaron O. Bailey, Jeffrey Shabanowitz, Donald F. Hunt, Benjamin A. Garcia, Ben E. Black and Lars E.T Jansen (2017) A dual inhibitory mechanism sufficient to maintain cell cycle restricted CENP-A assembly. Molecular Cell, 65: 231–246
     
  2. Aimee M Deaton, Mariluz Gomez-Rodriguez, Jakub Mieczkowski, Michael Y Tolstorukov, Sharmistha Kundu, Ruslan I Sadreyev, Lars E.T. Jansen and Robert E Kingston (2016) Enhancer regions show high histone H3.3 turnover that changes during differentiation eLife, 5:e15316
     
  3. Dani L. Bodor, João F. Mata, Mikhail Sergeev, Ana Filipa David, Kevan J. Salimian, Tanya Panchenko, Don W. Cleveland, Ben E. Black, Jagesh V. Shah and Lars E.T. Jansen (2014) The quantitative architecture of centromeric chromatin. eLife, 2014;3:e02137
     
  4. Dani L. Bodor, Luis P. Valente, João F. Mata, Ben E. Black and Lars E.T. Jansen (2013) Assembly in G1 phase and Long-Term Stability are Unique Intrinsic Features of CENP-A nucleosomes. Mol. Biol. Cell., 24: 923-932
     
  5. Mariana C.C. Silva, Dani L. Bodor, Madison E. Stellfox, Nuno M.C. Martins, Helfrid Hochegger, Daniel R. Foltz and Lars E.T. Jansen (2012) Cdk activity couples epigenetic centromere inheritance to cell cycle progression. Developmental Cell, 22: 52-63
More Publications...

Research Images

We focus on different functional domains of the genome, each of which display epigenetic behavior but likely through different mechanisms. These include the centromere (the site of chromosome attachment to the mitotic apparatus, ensuring their segregation during cell division), as well as actively transcribed chromatin and silent chromatin. How are these domains formed and then stably maintained?

 

How is chromatin inherited across the cell cycle? Nucleosomes face several challenges during cell division including DNA replication that disrupts histone DNA contacts and leads to nucleosome loss. Mechanisms must exist that maintain nucleosomes and render them heritable.
 

 


Centromeres, a paradigm for epigenetic inheritance. Much of our work focuses on the centromere, a unique chromatin domain connecting chromosomes to the mitotic spindle during mitosis. The centromere is maintained epigenetically through the propagation of a specialized chromatin structure that is not determined directly by the underlying DNA sequences. Instead, a unique histone H3 variant, CENP-A (red foci) marks the site of the centromere and is critical for its epigenetic propagation.
 

Contact: lars.jansen@bioch.ox.ac.uk
Graduate Student and Postdoctoral Positions: We are always on the lookout for talented, driven scientist at all levels. For enquiries please send your CV and motivation to Lars Jansen, lars.jansen@bioch.ox.ac.uk
Website: http://www.jansenlab.org