Take, Remember, Give Back: The Potential of Z-DNA as a Carrier of Epigenetic Memory

Take, Remember, give back: The potential of Z-DNA as a carrier of epigenetic memory. Epigenetic memory is immensely powerful in biological systems, giving stable memory of gene expression states over many cell generations, long after the initial signal that switched the gene on or off has disappeared. The current dogma, based on correlations and indirect evidence, invokes covalently modified histone tails as the molecular carriers of epigenetic memory. However, histones themselves must be completely removed from DNA during transcription and replication, and are heavily remodified throughout mitosis. This project suggests that modification of histone tails is a secondary event, and is not the true molecular driving force for epigenetic memory. The hypothesis is that it is the DNA itself which is both the sensor of gene expression and the carrier of epigenetic memory. The project intends to show that the structure responsible is the left-handed "Z-DNA" conformation, which twists in the opposite direction to the right-handed "B-DNA" double helix. The project proposes a combination of computational prediction of DNA properties, in vitro physical assays for DNA structure, and quantitative in vivo analysis probably leading to prediction of the epigenetic memory potential of specific loci based on DNA sequence alone.

Principal investigators
Ringrose, Leonie Helen Prof. Dr. (Details) (Quantitative Biology of the Eukaryotic Cell)

Volkswagen-Stiftung (VW)

Duration of project
Start date: 04/2018
End date: 03/2020

Research Areas
Life Sciences

Last updated on 2022-09-09 at 03:05