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Distinct contributions of KAT2A histone acetyl-transferase complexes to human erythropoiesis

ABSTRACT: Distinct contributions of KAT2A histone acetyl-transferase complexes to human erythropoiesis

PROVIDER: PRJNA527967 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8749830.fastq.gz	Fastqsanger.gz
	SRR8749831.fastq.gz	Fastqsanger.gz
	SRR8749832.fastq.gz	Fastqsanger.gz
	SRR8749833.fastq.gz	Fastqsanger.gz
	SRR8749834.fastq.gz	Fastqsanger.gz

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Distinct contributions of KAT2A histone acetyl-transferase complexes to human erythropoiesis

Project description:KAT2A is a histone acetyl-transferase involved in stabilization of transcriptional activity through acetylation of lysine residue 9 of Histone 3. Mouse knockout models suggest that Kat2a is dispensable for haematopoietic stem and progenitor cell activity, despite a central role in survival and maintenance of Acute Myekoid Leukaemia cells through block of differentiation. Herein, we investigate KAT2A activity in human cord blood haematopoiesis and identify a specific requirement in the establishment of the erythroid lineage. KAT2A is required for specification and survival of Erythroid-Megakaryocytic progenitors, with regulation of expression of the erythropoietin receptor (EPOR) gene, which participates in lineage commitment, as well as of later effector genes in the platelet and erythroid lineages. Early and late lineage roles can be distinctly attributed to the ATAC and SAGA complexes in which context KAT2A exerts its activity. ATAC is active earlier in erythroid lineage development and mediates MEP specification from HSC, whilst SAGA activity is required post-commitment, including in expression of haemoglobin genes. We thus position KAT2A as a novel regulator of human erythropoiesis and separate early and later effects in lineage development with complex specificity. This has implications for putative therapeutic targeting of KAT2A complexes in leukaemia.

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Distinct contributions of KAT2A histone acetyl-transferase complexes to human erythropoiesis [RNA-seq]

Project description:Distinct contributions of KAT2A histone acetyl-transferase complexes to human erythropoiesis [RNA-seq]

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Project description:We report EGFR activation induces ERK-mediated S267 phosphorylation of acetyl-CoA synthetase 2 (ACSS2) and its subsequent nuclear translocation and complex formation with lysine acetyltransferase 2A (KAT2A).Consequently, KAT2A acts as a lactyltransferase to lactylate histone H3, leading to expression of Wnt/β-catenin, NFκB, and PD-L1, and brain tumor growth and immune evasion.

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