Biology subjects

Herzig, A.

Publications and source records attributed to Herzig, A..

4 recordsLinked to original sources

bioRxiv2025

Reversible repression of inducible genes by Polycomb Repressive Complex 2 and H3K27me3 in Drosophila melanogaster

The Polycomb system maintains cell fate decisions by establishing silenced chromatin at developmental regulators. This is mediated by histone H3 lysine 27 trimethylation (H3K27me3) deposited in highly modified chromatin domains by Polycomb repressive complex 2 (PRC2). Increasing evidence suggests that the Polycomb system has functions beyond developmental regulation but the underlying mechanisms remained unclear. Here, we show that large regions of the genome are moderately modified by H3K27me3 and transcriptionally repressed through PRC2. In contrast to genes in silenced chromatin, moderately modified genes remain inducible by physiological stimuli and the repressive function of PRC2 is balanced by activating inputs from the Trithorax system. This demonstrates a pervasive function of the Polycomb system in dynamically regulating homeostatic expression and inducibility of genes in differentiated cells. One-Sentence SummaryLarge regions of the genome are reversibly repressed by the Polycomb system, which prevents gene activation by low-level stimulation but maintains inducibility.

cell biology↗

bioRxiv2021

Haemocytes are critical for Drosophila melanogaster post-embryonic development, independent of control of the microbiota

Proven roles for haemocytes (blood cells) have expanded beyond the control of infections in Drosophila. Despite this, the critical role of haemocytes in post-embryonic development has long been thought to be limited to control of microorganisms during metamorphosis. This has previously been shown by rescue of adult development in haemocyte-ablation models under germ-free conditions. Here we show that haemocytes have a critical role in post-embryonic development beyond their ability to control the microbiota. Using a newly generated, strong haemocyte-specific driver line for the GAL4/UAS system, we show that specific ablation of haemocytes is pupal lethal, even under axenic conditions. Genetic rescue experiments prove that this is a haemocyte-specific phenomena. RNA-seq data suggests that dysregulation of the midgut is a critical consequence of haemocyte ablation. We believe this novel role of haemocytes during metamorphosis is a major finding for the field. This is an exciting new Drosophila model to study the precise mechanisms in which haemocytes regulate tissue development, findings from which could have far reaching implications beyond invertebrate biology. Summary StatementHaemocyte-ablation in Drosophila melanogaster with a strong haemocyte-specific driver causes pupal lethality

developmental biology↗

bioRxiv2021

Histone H3 Clipping is a novel signature of Human Neutrophil Extracellular Traps

Neutrophils are critical to host defence, executing diverse strategies to perform their antimicrobial and regulatory functions. One tactic is the production of neutrophil extracellular traps (NETs). In response to certain stimuli neutrophils decondense their lobulated nucleus and release chromatin into the extracellular space through a process called NETosis. However, NETosis, and the subsequent degradation of NETs, can become dysregulated. NETs are proposed to play a role in infectious as well as many non-infection related diseases including cancer, thrombosis, autoimmunity and neurological disease. Consequently, there is a need to develop specific tools for the study of these structures in disease contexts. In this study, we identified a NET-specific histone H3 cleavage event and harnessed this to develop a cleavage site-specific antibody for the detection of human NETs. By microscopy, this antibody distinguishes NETs from chromatin in purified and mixed cell samples. It also detects NETs in tissue sections. We propose this antibody as a new tool to detect and quantify NETs.

immunology↗

bioRxiv2020

Evaluation of saliva as a source of accurate whole-genome and microbiome sequencing data

This study sets out to establish the suitability of saliva-based whole-genome sequencing (WGS) through a comparison against blood-based WGS. To fully appraise the observed differences, we developed a novel technique of pseudo-replicates. We also investigated the potential of characterising individual salivary microbiomes from non-human DNA fragments found in saliva. We observed the majority of discordant genotype calls between blood and saliva calls fell into known regions of the human genome that are typically sequenced with low confidence; and could be identified by quality control measures. Pseudo-replication demonstrated that the levels of discordance between blood- and saliva-derived WGS data were entirely similar to what one would expect between technical replicates if an individuals blood or saliva had been sequenced twice. Finally, we successfully sequenced salivary microbiomes in parallel to human genomes as demonstrated by a comparison against the Human Microbiome Project. Author SummaryDNA is usually collected from blood for the analysis of human genomes. In France, a new and very large genetic dataset will be created where selected participants will be sent saliva-collection kits in the post as this data collection method presents numerous logistical benefits. It has been previously shown that good quality genetic data can be created from saliva, though existing studies have often not considered the latest technologies or have only analysed a very small number of individuals. In this study, we have analysed genetic data derived from saliva for 39 individuals to give a firm conclusion that the proposed genome sequencing approach of the new French dataset will be capable of provided high quality data by making a comparison to pre-existing genetic data derived from blood for these 39 individuals. In order to do so, we developed a novel method (presented here) to establish the similarity between two sets of genetic data for the same individual that are generated from separate DNA samples. Finally, we have also demonstrated an added bonus of colleting saliva samples: that it is possible to gather both human genetic data and potentially interesting salivary microbiome data at the same time by separating and analysing in parallel human and non-human DNA fragments.

genetics↗