bioRxiv Science⌕ Search

Biology subjects

Streeck, R.

Publications and source records attributed to Streeck, R..

3 recordsLinked to original sources

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↗

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↗

Linker Histone H1 subtypes specifically regulate neutrophil differentiation

Neutrophils are important innate immune cells that tackle invading pathogens with different effector mechanisms. They acquire this antimicrobial potential during their maturation in the bone marrow, where they differentiate from hematopoietic stem cells in a process called granulopoiesis. Mature neutrophils are terminally differentiated and short-lived with a high turnover rate. Here, we show a critical role for linker histone H1 on the differentiation and function of neutrophils using a genome-wide CRISPR/Cas9 screen in the human cell line PLB-985. We systematically disrupted expression of somatic H1 subtypes to show that individual H1 subtypes affect PLB-985 maturation in opposite ways. Importantly, H1 subtypes also affect neutrophil differentiation of murine bone marrow stem cells, demonstrating an unexpected subtype-specific role for H1 in granulopoiesis.

immunology↗