Chromatin-based epigenetic inheritance
Abstract: The genome is propagated through cell division cycles by the faithful duplication and segregation of chromosomes into two new daughter cells during mitotic divisions.
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 inheritance 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.
My lab aims at three major questions
- What is the basis of chromatin-based memory at the human centromere? The histone H3 variant CENP-A is critical for the faithful inheritance and propagation of centromeres and is dependent on the stable transmission and self-templating capacity of CENP-A chromatin.
- Can chromatin contribute to the maintenance of active gene expression? We have developed methods to directly determine the rate of histone H3.1 and H3.3 retention at specific loci in human somatic cells and aim to determine their contribution to transcriptional memory. Finally, 3) we use heritable gene silencing in yeast to determine whether and how epigenetic states can impact on the evolution of a species.