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Histone acetyltransferase Kat2a stabilises pluripotency with control of transcriptional heterogeneity

ABSTRACT: Histone acetyltransferase Kat2a stabilises pluripotency with control of transcriptional heterogeneity

PROVIDER: PRJNA472639 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7207350.fastq.gz	Fastqsanger.gz
	SRR7207343.fastq.gz	Fastqsanger.gz
	SRR7207344.fastq.gz	Fastqsanger.gz
	SRR7207345.fastq.gz	Fastqsanger.gz
	SRR7207346.fastq.gz	Fastqsanger.gz

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Histone acetyltransferase Kat2a stabilises pluripotency with control of transcriptional heterogeneity

Project description:Cell fate transitions in mammalian stem cell systems have often been associated with transcriptional heterogeneity, however existing data have failed to establish a functional or mechanistic link between the two phenomena. Experiments in unicellular organisms support the notion that transcriptional heterogeneity can be used to facilitate adaptability to environmental changes and have identified conserved chromatin-associated factors that modulate levels of transcriptional noise. By inhibiting the paradigmatic histone acetyl-transferase, and candidate noise modulator, Kat2a (yeast orthologue Gcn5) in mouse embryonic stem cells, we show destabilisation of pluripotency-associated gene regulatory networks through increased global and locus-specific transcriptional heterogeneity. Functionally, network destabilisation associates with reduced pluripotency and accelerated mesendodermal differentiation, with increased probability of transitions into lineage commitment. Thus, we functionally link transcriptional heterogeneity to cell fate transitions through manipulation of the histone acetylation landscape of mouse embryonic stem cells and establish a general paradigm that could be exploited in other normal and malignant stem cell fate transitions.

2019-01-20 | GSE114797 | GEO

Histone Acetyltransferase KAT2A Stabilizes Pluripotency with Control of Transcriptional Heterogeneity.

Project description:Cell fate transitions in mammalian stem cell systems have often been associated with transcriptional heterogeneity; however, existing data have failed to establish a functional or mechanistic link between the two phenomena. Experiments in unicellular organisms support the notion that transcriptional heterogeneity can be used to facilitate adaptability to environmental changes and have identified conserved chromatin-associated factors that modulate levels of transcriptional noise. Herein, we show destabilization of pluripotency-associated gene regulatory networks through increased transcriptional heterogeneity of mouse embryonic stem cells in which paradigmatic histone acetyl-transferase, and candidate noise modulator, Kat2a (yeast orthologue Gcn5), have been inhibited. Functionally, network destabilization associates with reduced pluripotency and accelerated mesendodermal differentiation, with increased probability of transitions into lineage commitment. Thus, we show evidence of a relationship between transcriptional heterogeneity and cell fate transitions through manipulation of the histone acetylation landscape of mouse embryonic stem cells, suggesting a general principle that could be exploited in other normal and malignant stem cell fate transitions. Stem Cells 2018;36:1828-11.

| S-EPMC6334525 | biostudies-literature

Divergent Functions of Histone Acetyltransferase Paralogs KAT2A and KAT2B in Keratinocyte Stemness and Differentiation

Project description:The mammalian epidermis undergoes constant renewal replenished by a pool of stem cells and terminal differentiation of their progeny. This is accompanied by changes in gene expression and morphology orchestrated, in part, by epigenetic modifiers. Here, we defined the role of histone acetyltransferase KAT2A in epidermal homeostasis and provided a comparative analysis that revealed key functional divergence with its paralogue, KAT2B. In contrast to KAT2B's reported function in epidermal differentiation, KAT2A supports the undifferentiated state in keratinocytes. RNA-seq analysis of KAT2A- and KAT2B- depleted keratinocytes revealed dysregulated epidermal differentiation. Depletion of KAT2A led to premature expression of epidermal differentiation genes in the absence of inductive signals, whilst loss of KAT2B delayed differentiation. KAT2A acetyltransferase activity was indispensable in regulating epidermal differentiation gene expression. The metazoan-specific N-terminus of KAT2A was also required to support its function in keratinocytes. We further showed that the interplay between KAT2A- and KAT2B- mediated regulation was important for normal cutaneous wound healing in vivo. Overall, these findings reveal a distinct mechanism in which keratinocytes utilize a pair of highly homologous histone acetyltransferases to support divergent functions in self-renewal and differentiation processes.

2023-06-09 | GSE215244 | GEO

ACSS2-coupled KAT2A regulates histone H3 lactylation in gene promoter regions and gene expression

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.

2024-10-01 | GSE278139 | GEO

Transcriptomic changes in HCT116 cells after KAT2A knockout

Project description:We were interested in transcriptional changes after depletion of histone acetyltransferase KAT2A in human colorectal cancer. Therefore, we utilized HCT116 cells as model, and analyzed global alterations of gene expression.

2024-11-01 | GSE246881 | GEO

Divergent Functions of Histone Acetyltransferase Paralogs KAT2A and KAT2B in Keratinocyte Stemness and Differentiation

Project description:Divergent Functions of Histone Acetyltransferase Paralogs KAT2A and KAT2B in Keratinocyte Stemness and Differentiation

| PRJNA889419 | ENA

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.

2021-09-28 | GSE128512 | GEO

Kat2a regulates hippocampal memory formation [RNA-seq]

Project description:We sequenced mRNA from 24 samples extracted from mouse CA1 tissue to generate the first CA1-specific murine transcriptome and the first CA1-transcriptome in response to environmental novelty under normal and Kat2a-loss-of-function conditions. Samples were divded in 4 groups: A: Control naM-CM-/ve (n=6), B: control novelty-exposed (n=5), C: Kat2a cKO naM-CM-/ve (n=6), D: Kat2a cKO novelty-exposed (n=7). Pairwise comparisons for AvsB, AvsC, BvsD and CvsD were performed using DESeq2.

2014-07-16 | E-GEOD-53380 | biostudies-arrayexpress

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

2021-09-28 | GSE128902 | GEO

Transcriptomic changes in CRC1 and CRC2 patient-derived CRC 3D models after CRISPRi-based KAT2A knockdown

Project description:We were interested in transcriptional changes after depletion of histone acetyltransferase KAT2A in human colorectal cancer. Therefore, we utilized patient-derived CRC 3D spheroids CRC1 and CRC2 as models, and analyzed global alterations of gene expression.

2025-03-28 | GSE287741 | GEO

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