Biology subjects

Fischer, V.

Publications and source records attributed to Fischer, V..

3 recordsLinked to original sources

bioRxiv2022

Global ecomorphological restructuring of dominant marine reptiles prior to the K/Pg mass extinction

Mosasaurid squamates were the dominant amniote predators in marine ecosystems during most of the Late Cretaceous. Evidence from multiple sites worldwide of a global mosasaurid community restructuring across the Campanian-Maastrichtian transition may have wide-ranging implications for the evolution of diversity of these top oceanic predators. In this study, we use a suite of biomechanical traits and functionally descriptive ratios to investigate how the morphofunctional disparity of mosasaurids evolved through time and space prior to the Cretaceous-Palaeogene (K/Pg) mass extinction. Our results suggest that the worldwide taxonomic turnover in mosasaurid community composition from Campanian to Maastrichtian is reflected by a notable increase in morphofunctional disparity on a global scale, but especially driven the North American record. Ecomorphospace occupation becomes more polarised during the late Maastrichtian, as the morphofunctional disparity of mosasaurids plateaus in the Southern Hemisphere and decreases in the Northern Hemisphere. We show that these changes are not associated with strong modifications in mosasaurid size, but rather with the functional capacities of their skulls, and that mosasaurid morphofunctional disparity was in decline in several provincial communities before the K-Pg mass extinction. Our study highlights region-specific patterns of disparity evolution, and the importance of assessing vertebrate extinctions both globally and regionally. Ecomorphological differentiation in mosasaurid communities, coupled with declines in other formerly abundant marine reptile groups, indicates widespread restructuring of higher trophic levels in marine food webs was well underway when the K-Pg mass extinction took place.

paleontology↗

bioRxiv2021

SUPT3H-less SAGA coactivator can assemble and function without significantly perturbing RNA polymerase II transcription in mammalian cells

Coactivator complexes regulate chromatin accessibility and transcription. SAGA (Spt-Ada-Gcn5 Acetyltransferase) is an evolutionary conserved coactivator complex. The core module scaffolds the entire SAGA complex and adopts a histone octamer-like structure, which consists of six histone fold domain (HFD)-containing proteins forming three histone fold (HF) pairs, to which the double HFD-containing SUPT3H adds an HF pair. Spt3, the yeast ortholog of SUPT3H, interacts genetically and biochemically with the TATA binding protein (TBP) and contributes to global RNA polymerase II (Pol II) transcription. Here we demonstrate that i) SAGA purified from human U2OS or mouse embryonic stem cells (mESC) can assemble without SUPT3H; ii) SUPT3H is not essential for mESC survival, iii) SUPT3H is required for mESC growth and self-renewal, and iv) the loss of SUPT3H from mammalian cells affects the transcription of only a specific subset of genes. Accordingly, in the absence of SUPT3H no major change in TBP accumulation at gene promoters was observed. Thus, SUPT3H is not required for the assembly of SAGA, TBP recruitment, or overall Pol II transcription, but plays a role in mESC growth and self-renewal. Our data further suggest that yeast and mammalian SAGA complexes contribute to transcription regulation by distinct mechanisms.

molecular biology↗

bioRxiv2021

Histone H2Bub1 deubiquitylation is essential for mouse development, but does not regulate global RNA polymerase II transcription

Co-activator complexes dynamically deposit post-translational modifications (PTMs) on histones, or remove them, to regulate chromatin accessibility and/or to create/erase docking surfaces for proteins that recognize histone PTMs. SAGA (Spt-Ada-Gcn5 Acetyltransferase) is an evolutionary conserved multisubunit co-activator complex with modular organization. The deubiquitylation module (DUB) of mammalian SAGA complex is composed of the ubiquitin-specific protease 22 (USP22) and three adaptor proteins, ATXN7, ATXN7L3 and ENY2, which are all needed for the full activity of the USP22 enzyme to remove monoubiquitin (ub1) from histone H2B. Two additional USP22-related ubiquitin hydrolases (called USP27X or USP51) have been described to form alternative DUBs with ATXN7L3 and ENY2, which can also deubiquitylate H2Bub1. Here we report that USP22 and ATXN7L3 are essential for normal embryonic development of mice, however their requirements are not identical during this process, as Atxn7l3-/- embryos show developmental delay already at embryonic day (E) 7.5, while Usp22-/- embryos are normal at this stage, but die at E14.5. Global histone H2Bub1 levels were only slightly affected in Usp22 null embryos, in contrast H2Bub1 levels were strongly increased in Atxn7l3 null embryos and derived cell lines. Our transcriptomic analyses carried out from wild type and Atxn7l3-/- mouse embryonic stem cells (mESCs), or primary mouse embryonic fibroblasts (MEFs) suggest that the ATXN7L3-related DUB activity regulates only a subset of genes in both cell types. However, the gene sets and the extent of their deregulation were different in mESCs and MEFs. Interestingly, the strong increase of H2Bub1 levels observed in the Atxn7l3-/- mESCs, or Atxn7l3-/- MEFs, does not correlate with the modest changes in RNA Polymerase II (Pol II) occupancy and lack of changes in Pol II elongation observed in the two Atxn7l3-/- cellular systems. These observations together indicate that deubiquitylation of histone H2Bub1 does not directly regulate global Pol II transcription elongation.

molecular biology↗