Chromatin structure and epigenetic regulation

Chromatin is the structural framework that packages and organizes DNA within cells. In eukaryotes, its basic unit, the nucleosome, consists of DNA wrapped around an octamer of core histone proteins, with neighbouring nucleosomes connected by linker DNA. Linker histones further compact chromatin, playing a key role in gene regulation.

Our research focuses on how epigenetic factors – particularly histone variants and post-translational modifications (PTMs) such as acetylation – influence chromatin structure and function.

In recent years our lab has investigated:

  • the binding of linker histones to nucleosomes and their role in reducing linker DNA flexibility [1]
  • how nucleosome arrays bound by linker histones transition between open and compact states, revealing key insights into chromatin structural dynamics [2]
  • the impact of CENP-A, a histone H3 variant that epigenetically defines the centromere, affects the dynamic flexibility of nucleosomal DNA [3]
  • how pioneer transcription factors (PTFs) overcome epigenetic repression caused by nucleosome positioning and DNA methylation, shedding light on gene activation mechanisms [4],[5]
  • the role of housekeeping enzyme NME1 in linking metabolism and epigenetic regulation, identifying it as a key regulator of acetyl-CoA availability for histone acetylation [6]

Publications:
[1] Bednar et al., Structure and dynamics of a 197 base-pair nucleosome in complex with linker histone H1. Mol Cell 2017, 66:384-397
[2] Garcia-Saez et al., Structure of an H1-bound 6-nucleosome array reveals an untwisted two-start chromatin fiber conformation. Mol Cell 2018, 72:902-915
[3] Boopathi et al., Phase-plate cryo-EM structure of the Widom 601 CENP-A nucleosome core particle reveals differential flexibility of the DNA ends. Nucleic Acids Res 2020, 48:5735-5748
[4] Bernaudat et al., Structural basis of DNA methylation-dependent site selectivity of the Epstein-Barr virus lytic switch protein ZEBRA/Zta/BZLF1. Nucleic Acids Res 2022, 50:490-511
[5] Ozden B et al., Molecular Mechanism of Nucleosome Recognition by the Pioneer Transcription Factor Sox. J Chem Inf Model 2023, 63:3830-3853
[6] Iuso et al., Nucleoside Diphosphate Kinases 1 and 2 regulate a liver protective response to a high-fat diet. Sci Adv 2023, 9(36):eadh0140