The disruption of histone PTMs is a required event for environmentally-induced transgenerational germline dysfunctions

Abstract Authors: Patrick Allard1,2
1. Institute for Society and Genetics, UCLA, Los Angeles, CA. USA.
2. Molecular Biology Institute, UCLA, Los Angeles, CA. USA.

Abstract Text:

The overarching goal of our research program is to dissect the epigenetic and metabolic programs that encode and transmit a memory of environmental exposure for several generations. In that context, we aim to understand how environmental influences alter the reproductive program of organisms in a transgenerational fashion and what makes the germline a particularly important and sensitive target of these exposures.

Here, we will present our latest work on the inter and transgenerational disruption of germline function caused by exposure to two model toxicants: the plastic manufacturing chemical and endocrine disruptor Bisphenol A as well as ethanol. We combine the tractability and conservation of the model system C. elegans with state-of-the-art epigenomic analyses, classical genetics and cytological approaches to shed light on the mechanisms of germline apoptosis caused at the F1 and F3 generations following exposures. We show that germline homeostasis is controlled by the interplay between changes in the levels and distribution of histone post-translational modifications (PTMs) in the germline caused by these exposures and the activation of the meiotic checkpoints. Together, these experiments show that the deregulation of the fine tuning of histone PTMs in the germline is a required event for the inter- and trans-generational germline dysfunctions caused by various environmental exposures.