Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effects of histone acetyltransferase dead mutation of KAT6A and KAT6B on gene expression in E9.5 mouse embryos and E14.5 mouse foetal liver hematopoietic cells

ABSTRACT: The paralogous histone acetyltransferases KAT6A and KAT6B are large 200 kDa proteins of identical protein domain structure with high sequence similarity within the functional protein domains. Kat6a and Kat6b null mutation have severe effects on mouse embryonic and foetal development as well as on adult stem cell populations. Apart from the well-defined MYST family histone acetyltransferase domain, the proteins have N-terminal winged-helix domains followed by tandem plant homeodomain fingers preceding the histone acetyltransferase domain, as well as a long unstructured acidic region and serine and methionine rich regions following the histone acetyltransferase domain. In this study we examined the effects of point mutations that reduce the histone acetyltransferase function to background levels on gene expression in E9.5 mouse embryos and E14.5 mouse foetal liver haematopoietic cells and compared these to the effects of the null mutations of the Kat6a and Kat6b gene.

ORGANISM(S): Mus musculus

PROVIDER: GSE318436 | GEO | 2026/05/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Effects of loss and gain of KAT6B on gene expression in the developing cerebral cortex [Myst4_RNAseq]

Project description:High histone acetylation is associated with high transcriptional activity. The lysine acetyltransferase KAT6B is known to be required for histone acetylation and KAT6B is essential for normal brain development. In this study we examined the effects of loss and gain of KAT6B on gene expression in the developing cerebral cortex. We isolated RNA from the dorsal telencephalon of embryonic day 12.5 embryos, which is the primordium of the cerebral cortex, and from the E15.5 foetal cortex of mouse embryos and foetuses that lacked KAT6B or overexpressed KAT6B. Genes required for brain development and neuronal differentiation were downregulated in Kat6b null tissues and upregulated in Kat6b transgenic overexpressing tissue.

2024-11-06 | GSE280784 | GEO

The histone acetyltransferase KAT6B is required for haematopoietic stem cell development and function

Project description:The histone lysine acetyltransferase KAT6B (MYST4, MORF, QKF) is the target of recurrent chromosomal translocations causing haematological malignancies with poor prognosis. Using Kat6b germline deletion and overexpression in mice, we determined the role of KAT6B in the haematopoietic system. We found that KAT6B sustained the fetal haematopoietic stem cell pool but did not affect viability or differentiation. KAT6B was essential for normal levels of histone H3 lysine 9 (H3K9) acetylation but not for a previously proposed target, H3K23. Compound heterozygosity of Kat6b and the closely related gene, Kat6a, abolished haematopoietic reconstitution after transplantation. KAT6B and KAT6A cooperatively promoted transcription of genes regulating haematopoiesis, including the Hoxa cluster, Pbx1, Meis1, Gata family, Erg and Flt3. In conclusion, we identified the haematopoietic processes requiring Kat6b and showed that KAT6B and KAT6A synergistically promoted HSC development, function and transcription. Our findings are pertinent to current clinical trials testing KAT6A/B inhibitors as cancer therapeutics.

2024-02-25 | GSE256039 | GEO

KAT6B overexpression rescues embryonic lethality in homozygous null KAT6A mice restoring vitality and normal lifespan [CUT&TAG]

Project description:Closely related genes typically display common essential functions but also functional diversification, ensuring retention of both genes throughout evolution. The histone lysine acetyltransferases KAT6A (MOZ) and KAT6B (QKF/MORF), sharing identical protein domain structure, are mutually exclusive catalytic subunits of a multiprotein complex. Mutations in either KAT6A or KAT6B result in congenital intellectual disability disorders in human patients. In mice, loss of function of either gene results in distinct, severe phenotypic consequences. In this dataset, we investigate the effects of overexpression of KAT6B on the histone acetylation changes caused by loss of KAT6A in mouse embryonic fibroblasts. We show that Kat6b overexpression restores acetylation at histone H3 lysines 23 in Kat6a mutant mouse primary embryonic fibroblasts.

2025-02-24 | GSE287243 | GEO

KAT6B overexpression rescues embryonic lethality in homozygous null KAT6A mice restoring vitality and normal lifespan [RNA-seq]

Project description:Closely related genes typically display common essential functions but also functional diversification, ensuring retention of both genes throughout evolution. The histone lysine acetyltransferases KAT6A (MOZ) and KAT6B (QKF/MORF), sharing identical protein domain structure, are mutually exclusive catalytic subunits of a multiprotein complex. Mutations in either KAT6A or KAT6B result in congenital intellectual disability disorders in human patients. In mice, loss of function of either gene results in distinct, severe phenotypic consequences. In this dataset, we investigate the effects of overexpression of KAT6B on the gene expression changes caused by loss of KAT6A in mouse E9.5 embryos. We show that Kat6b overexpression reverses critical gene expression anomalies in Kat6a mutant embryos.

2025-02-24 | GSE287244 | GEO

Effects of loss and gain of KAT6B on gene expression in neural stem and progenitor cells [NSC_Kat6b_RNAseq]

Project description:High histone acetylation is associated with high transcriptional activity. The lysine acetyltransferase KAT6B is known to be required for histone acetylation and KAT6B is essential for normal brain development. In this study we examined the effects of loss and gain of KAT6B on gene expression in forebrain neural stem and progenitor cells (NSPCs). We isolated NSPCs from the dorsal telencephalon of embryonic day 12.5 embryos, which is the primordium of the cerebral cortex, from mouse embryos that lacked KAT6B or overexpressed KAT6B. We cultured the cells in vitro for 3 to 5 passages before isolating RNA for library production and RNA-sequencing. We found that genes required for neuronal differentiation and brain development were downregulated in Kat6b null cells and upregulated in Kat6b transgenic overexpressing cells.

2024-11-06 | GSE280783 | GEO

Effects of loss and gain of the histone acetyltransferase KAT6B on DNA accessibility (ATAC-seq)

Project description:Heterozygous mutations in the histone acetyltransferase gene KAT6B (MYST4/MORF/QKF) cause cognitive disorders. Congruently, KAT6B is required for brain development, neural stem cell self-renewal and neuronal differentiation in mice. Despite the clear requirement for KAT6B in brain development, its molecular roles remain unexplored. Here we use ATAC sequencing to determine the effects of loss or gain of KAT6B on DNA accessiblity.

2024-11-06 | GSE267675 | GEO

Epigenetic effects (H3K9ac, H3K14ac, H3K23ac and Pol II) of Kat6b loss in mouse neural stem cells (CUT&Tag)

Project description:Heterozygous mutations in the histone acetyltransferase gene KAT6B (MYST4/MORF/QKF) cause cognitive disorders. Congruently, KAT6B is required for brain development, neural stem cell self-renewal and neuronal differentiation in mice. Despite the clear requirement for KAT6B in brain development, its molecular roles remain unexplored. Here we use CUT&Tag sequencing to determine the effects of loss or gain of KAT6B on H3K9ac and H3K23ac histone marks and on RNA Pol II.

2024-11-06 | GSE267672 | GEO

RNA sequeqncing data of Kat6a–/–, Kat6a+/– and Kat6a+/+ E12.5 dorsal telencephalon and of Kat6a+/– and Kat6a+/+ E16.5 cortical neurons

Project description:Mutation of one allele of the KAT6A gene encoding the histone acetyltransferase KAT6A (MOZ, MYST3) causes Arboleda-Tham-Syndrome (ARTHS), which is characterised by developmental delay, cognitive impairment and autism-like behaviours. We used mice to examine the effects of Kat6a mutations on gene expression in the develping cerebral cortex and cortical neurons. We examined the effects of homozygous and heterozygous loss of Kat6a on gene expression in the E12.5 dorsal telecencephalon, the embryonic precursor of the cerebral cortex, and the effects of heterozygous loss of Kat6a on gene expression in foetal cortical neurons.

2026-02-03 | GSE304794 | GEO

Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363 [BrU-Seq]

Project description:KAT6A, and its paralog KAT6B, are histone lysine acetyltransferases (HAT) that acetylate histone H3K23 and regulate diverse biological processes including transcription, cell-cycle progression, and stem cell development. KAT6A exerts an oncogenic role in several tumor types including breast cancer where it is amplified in 10-15% of patients. However, pharmacologic targeting of KAT6A to achieve therapeutic benefit has been a challenge. Here we describe identification of a highly potent, selective and orally bioavailable KAT6A/KAT6B inhibitor CTx-648 (PF-9363), derived from a novel benzisoxazole series, which demonstrates anti-tumor activity in correlation with H3K23Ac inhibition in KAT6A over-expressing breast cancer. Transcriptional and epigenetic profiling studies show reduced RNA Pol II binding and downregulation of genes involved in estrogen signaling, cell cycle and stem cell pathways associated with CTx-648 anti-tumor activity in ER-positive (ER+) breast cancer. CTx-648 treatment leads to potent tumor growth inhibition in ER+ breast cancer in vivo models, including models refractory to endocrine therapy, highlighting the potential for targeting KAT6A in ER+ breast cancer.

2023-06-05 | GSE233787 | GEO

Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363 [ATAC-Seq]

2023-06-05 | GSE233784 | GEO