How does epigenetic inheritance work?

- 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.

We work on aspects of all three of these themes.

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. how is chromatin inherited across the cell cycle?

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.

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.

Watching cells propagate centromeres

We use genome engineering, high-end molecular biology and microscopy to unravel the mechanisms of the CENP-A-based epigenetic feedback loop that drives centromere inheritance.