Biology subjects

Puthier, D.

Publications and source records attributed to Puthier, D..

3 recordsLinked to original sources

bioRxiv2024

ATAD2 drives HIRA/histone H3.3-dependent chromatin dynamics

ATAD2, a conserved protein which is predominantly expressed in embryonic stem (ES) cells and spermatogenic cells, emerges as a crucial regulator of chromatin plasticity. Our previous parallel studies conducted in both ES cells and S. pombe highlighted the fundamental role of ATAD2 in facilitating chromatin-bound histone chaperone turnover. Focusing on spermatogenesis, we demonstrate here that ATAD2 regulates the HIRA-dependent localization of H3.3 on the genome and influences H3.3-mediated gene transcription. Moreover, by modulating histone eviction and the assembly of protamines, ATAD2 ensures proper chromatin condensation and genome packaging in mature sperm. Disruption of Atad2 function in mice leads to abnormal genome organization in mature spermatozoa. Together, these findings establish a previously overlooked level of chromatin dynamic regulation, governed by ATAD2-controlled histone chaperones binding to chromatin, which defines the balance between histone deposition and removal.

developmental biology↗

bioRxiv2024

SciGeneX: Enhancing transcriptional analysis through gene module detection in single-cell and spatial transcriptomics data.

The standard pipeline to analyze scRNA-seq or spatial transcriptomics data focuses on a gene-centric approach, which overlooks the collective behavior of genes. However, cell populations should be viewed as intricate combinations of activated and repressed pathways. Thus, a broader view of gene behavior would provide more accurate information on cellular heterogeneity in single-cell or spatial transcriptomics data. Here, we described SciGeneX, a R package implementing a neighborhood analysis and a graph partitioning method to generate co-expression gene modules. These gene modules, which can be shared or restricted between cell populations, collectively reflect cell populations, and their combinations are able to highlight specific cell populations, even rare ones. SciGeneX was also able to uncover rare and novel cell populations which were not observed before in spatial transcriptomics data of human thymus. We show that SciGeneX outperforms existing methods on both artificial and experimental datasets. Overall, SciGeneX will aid in unraveling cellular and molecular diversity in single-cell and spatial transcriptomics studies. The R package is available at https://github.com/dputhier/scigenex.

bioinformatics↗

bioRxiv2023

Nucleoside Diphosphate Kinases 1 and 2 regulate a protective liver response to a high-fat diet

De novo lipogenesis (DNL), the process whereby cells synthesize fatty acids from acetyl-coenzyme A (acetyl-CoA), is deregulated in diverse pathologies, including cancer. Here we report that DNL is negatively regulated by Nucleoside Diphosphate Kinases 1 and 2 (NME1/2), housekeeping enzymes involved in nucleotide homeostasis that were recently discovered to bind co-enzyme A (CoA). We show that NME1 additionally binds acetyl-CoA and that ligand recognition involves a unique binding mode dependent on the CoA/acetyl-CoA 3 phosphate. We report that Nme2 knockout mice fed a high-fat diet (HFD) exhibit excessive triglyceride synthesis and liver steatosis. In liver cells NME2 mediates a gene transcriptional response to HFD leading to DNL repression and activation of a protective gene expression program via targeted histone acetylation. Our findings implicate NME1/2 in the epigenetic regulation of a protective liver response to HFD and suggest a potential role in controlling acetyl-CoA usage between the competing paths of histone acetylation and DNL.

molecular biology↗