A5005594568- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Endoplasmic Reticulum Stress and Disease
- Epigenetics and DNA Methylation
- Cellular transport and secretion
- Cancer-related gene regulation
- Cancer Research and Treatments
- Histone Deacetylase Inhibitors Research
- Genetics, Bioinformatics, and Biomedical Research
University of Leicester
2017-2022
Institut de Biologie Structurale
2016-2022
Centre National de la Recherche Scientifique
2020-2022
CEA Grenoble
2020-2022
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2020-2022
Université Grenoble Alpes
2017-2022
Institute of Structural and Molecular Biology
2021
Institut Laue-Langevin
2020
European Molecular Biology Laboratory
2018
Nuclear protein in testis (Nut) is a universal oncogenic driver the highly aggressive NUT midline carcinoma, whose physiological function male germ cells has been unclear. Here we show that expression of Nut normally restricted to post-meiotic spermatogenic cells, where its presence triggers p300-dependent genome-wide histone H4 hyperacetylation, which essential for completion histone-to-protamine exchange. Accordingly, inactivation induces sterility with spermatogenesis arrest at...
Histone modifications are deposited by chromatin modifying enzymes and read out proteins that recognize the modified state. BRD4-NUT is an oncogenic fusion protein of acetyl lysine reader BRD4 binds to acetylase p300 enables formation long-range intra- interchromosomal interactions. We here examine how acetylation reading writing enable such show NUT contains acidic transcriptional activation domain TAZ2 p300. use NMR investigate structure complex found has autoinhibitory role for NUT-TAZ2...
Abstract The transcriptional co-activator and acetyltransferase p300 is required for fundamental cellular processes, including differentiation growth. Here, we report that forms phase separated condensates in the cell nucleus. separation ability of regulated by autoacetylation relies on its catalytic core components, histone (HAT) domain, autoinhibition loop, bromodomain. sequester chromatin such as H3 tail DNA, are amplified through binding to nucleosome. HAT activity decreased due...
We present a combination of small-angle neutron scattering, deuterium labelling and contrast variation, temperature activation fluorescence spectroscopy as novel approach to obtain time-resolved, structural data individually from macromolecular complexes their substrates during active biochemical reactions. The allowed us monitor the mechanical unfolding green fluorescent protein model substrate by archaeal AAA+ PAN unfoldase on sub-minute time scale. Concomitant with its substrate, complex...
Small-angle neutron scattering (SANS), combined with macromolecular deuteration and solvent contrast variation (H 2 O/D O exchange) allows focussing selectively on the signal of specific proteins in multi-protein complexes or mixtures isolated proteins. We illustrate this unique capacity by example a functional protein-degradation system solution, PAN-20S proteasome complex presence protein substrate, ssrA-tagged GFP. By comparing experimental SANS data synthetic SAXS (small-angle X-ray...
The transcriptional co-activator and acetyltransferase p300 is required for fundamental cellular processes, including differentiation growth. Here, we report that forms phase separated condensates in the cell nucleus. separation ability of regulated by autoacetylation relies on its catalytic core, representing a rare example biomolecular occurred through structured regions - HAT domain, autoinhibition loop, bromodomain. sequester chromatin components, such as histone H3 tail DNA, are...
Summary Histone modifications are deposited by chromatin modifying enzymes and read out proteins that recognize the modified state. BRD4-NUT is an oncogenic fusion protein of acetyl lysine reader BRD4 binds to acetylase p300 enables formation long-range intra- interchromosomal interactions. We here examine how acetylation reading writing enable such show NUT contains acidic transcriptional activation domain TAZ2 p300. use NMR investigate structure complex found has autoinhibitory role for...
The proteasome system allows the elimination of functional or structurally impaired proteins. This includes degradation nascent peptides. In Archaea, how complex interacts with translational machinery remains to be described. Here, we characterized a small orphan protein, Q9UZY3 (UniProt ID), conserved in Thermococcales. protein was identified native pull-down experiments using regulatory (proteasome-activating nucleotidase [PAN]) as bait. X-ray crystallography and small-angle scattering...