Dataset Information

Ush regulates macrophage-specific gene expression, fatty acid metabolism and cell cycle progression and cooperates with dNuRD to orchestrate hematopoiesis

ABSTRACT: Ush regulates macrophage-specific gene expression, fatty acid metabolism and cell cycle progression and cooperates with dNuRD to orchestrate hematopoiesis

PROVIDER: PRJNA610279 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	SRR11237235.fastq.gz	Fastqsanger.gz
	SRR11237236.fastq.gz	Fastqsanger.gz
	SRR11237237.fastq.gz	Fastqsanger.gz
	SRR11237238.fastq.gz	Fastqsanger.gz
	SRR11237239.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 21

Similar Datasets

Project description:The generation and modulation of lineage-specific gene expression programmes that determine proliferation capacity, metabolic profile and cell type-specific activities at each stage of differentiation are crucial for metazoan development. Gene expression programmes are moulded by a complex interplay between sequence-specific transcription factors, cofactors and epigenetic regulators. Here, we study U-shaped (Ush), a genetically defined transcriptional cofactor that cooperates with GATA transcription factors during blood cell differentiation in Drosophila. We use a cell line that is derived from macrophage precursors to comprehensively analyse Ush function at the cellular level. Using genomewide approaches we reveal that Ush binds to thousands of promoters and enhancers that are enriched for GATA sites and that it is a major regulator of transcription. Ush controls the expression of at least three functionally distinct gene classes encoding proteins relevant to different aspects of macrophage differentiation: cell cycle regulators, key metabolic enzymes and proteins enabling macrophage-specific functions. Ush is essential to maintain proliferative capacity and coordinately regulates fatty acid degradation and synthesis. We employ complementary biochemical approaches to characterise the molecular mechanisms of Ush-mediated gene regulation. We uncover the existence of two major Ush isoforms. One of these, Ush-B, uses a short peptide sequence to bind the Nucleosome Remodeling and Deacetylation (NuRD) complex. We demonstrate that this mode of interaction is conserved between vertebrates and invertebrates. Remarkably, Ush-B/NuRD specifically contributes to the repression of macrophage-specific genes demonstrating that Ush isoforms and epigenetic regulators make differential contributions to Ush controlled transcription programmes. Finally, we use genetic methods to define Ush and NuRD function in the developing fly. Ush and NuRD regulate enhancer activity during macrophage differentiation and both cooperate to suppress the formation of lamellocytes. Our findings uncover how a transcriptional cofactor can coordinate distinct cellular activities (proliferation, metabolism and cell type-specific functions) that are relevant for differentiation and maintenance of cell type-specific phenotypes.

Dataset Information

Ush regulates macrophage-specific gene expression, fatty acid metabolism and cell cycle progression and cooperates with dNuRD to orchestrate hematopoiesis

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets