ArticlePLoS genetics2021
Ush regulates hemocyte-specific gene expression, fatty acid metabolism and cell cycle progression and cooperates with dNuRD to orchestrate hematopoiesis.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 17 citations in OpenAlex.
- Comparative transcriptomic profiling reveals metabolic and regulatory features of Drosophila melanogaster S2 cells relative to newly hatched larval tissues.Genes & genomics · 2026Article
- SRP/dGATAb modulates the ecdysone response bidirectionally via locus-specific regulatory landscape.Epigenetics & chromatin · 2025Article
- Hangover regulates gene expression by limiting NSL-mediated H4K16 acetylation.Nucleic acids research · 2025Article
- In-depth transcriptomic analysis of Anopheles gambiae hemocytes uncovers novel genes and the oenocytoid developmental lineage.BMC genomics · 2024Article
- Genomics analysis of Drosophila sechellia response to Morinda citrifolia fruit diet.G3 (Bethesda, Md.) · 2022Article
- bfc, a novel serpent co-factor for the expression of croquemort, regulates efferocytosis in Drosophila melanogaster.PLoS genetics · 2021Article
- CK1α protects WAVE from degradation to regulate cell shape and motility in the immune response.Journal of cell science · 2021Article
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The generation of lineage-specific gene expression programmes that alter proliferation capacity, metabolic profile and cell type-specific functions during differentiation from multipotent stem cells to specialised cell types is crucial for development. During differentiation gene expression programmes are dynamically modulated by a complex interplay between sequence-specific transcription factors, associated cofactors and epigenetic regulators. Here, we study U-shaped (Ush), a multi-zinc finger protein that maintains the multipotency of stem cell-like hemocyte progenitors during Drosophila hematopoiesis. Using genomewide approaches we reveal that Ush binds to promoters and enhancers and that it controls the expression of three gene classes that encode proteins relevant to stem cell-like functions and differentiation: cell cycle regulators, key metabolic enzymes and proteins conferring specific functions of differentiated hemocytes. We employ complementary biochemical approaches to characterise the molecular mechanisms of Ush-mediated gene regulation. We uncover distinct Ush isoforms one of which binds the Nucleosome Remodeling and Deacetylation (NuRD) complex using an evolutionary conserved peptide motif. Remarkably, the Ush/NuRD complex specifically contributes to the repression of lineage-specific genes but does not impact the expression of cell cycle regulators or metabolic genes. This reveals a mechanism that enables specific and concerted modulation of functionally related portions of a wider gene expression programme. Finally, we use genetic assays to demonstrate that Ush and NuRD regulate enhancer activity during hemocyte differentiation in vivo and that both cooperate to suppress the differentiation of lamellocytes, a highly specialised blood cell type. Our findings reveal that Ush coordinates proliferation, metabolism and cell type-specific activities by isoform-specific cooperation with an epigenetic regulator.
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