Spotlight

Lars presented a lecture at Teddy Hall on "Genes, Genetics and Epigenetics", December 2020, Oxford 

Lars wrote a lay blog on genetics and epigenetics for Teddy Hall, Oxford

Centromeric chromatin is remarkably constant in size. We discovered that the boundaries of this domain are controlled by heterochromatin. Loss of enzymes maintaining Histone H3 lysine 9 methylation results in a dramatic expansion of CENP-A chromatin and the appearance of new centromere loci. See our latest preprint for this exciting discovery. 

Here, we report the discovery of a unique set of histone modifications that mark "primed" chromatin are heritably maintained through mitotic cell divisions without continued transcription. These hold a memory of past exposure to interferon-gamma, priming cells for future activation of gene expression. 

We discovered that the transcription factor STAT1 induces a mitotically stable memory of exposure to interferon. This primes cells to future encounters with the cytokine. See our recent paper on this fascinating phenomenon. 

We developed a system to isolate a spontaneously formed neocentromere in the context of the complex human genome. Check out our paper on this fascinating piece of biology!

Wojek Siwek and Sahar Tehrani identify a set of clustered human genes that display long-term priming following activation by interferon-gamma. We discovered that local cohesin binding contributes to restricting memory. 

The first description of centromeres in human induced or natural pluripotent stem cells! Inês Milagre demonstrates centromeres in this key cell type have a reduced size and limited pool of CENP-B and CENP-A chromatin. 

Our Marina Murillo wrote a comprehensive viewpoint on how centromere research developed over the last four decades.  She explains how neocentromeres taught us about both genetic and chromatin-based elements driving centromere formation and inheritance. Read it here! 

Here, we identified a series of new proteins required to stably transmit CENP-A chromatin through cell division. Most critically, we uncover a SUMOylation cycle that is essential to maintain an intact centromere complex. 

In a dramatic departure from human centromeres and mammalian transcription we explored this key question in evolution in a wonderful collaboration with Lilia Perfeito @ Gulbenkian, Portugal. In Nature Ecology & Evolution we report how chromatin-based heritable gene silencing in a yeast population can accelerate adaption to a novel environment.