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

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

PROVIDER: PRJNA1211682 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32029855_1.fastq.gz	Fastqsanger.gz
	SRR32029855_2.fastq.gz	Fastqsanger.gz
	SRR32029856_1.fastq.gz	Fastqsanger.gz
	SRR32029856_2.fastq.gz	Fastqsanger.gz
	SRR32029857_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

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

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 [CUT&TAG]

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

| PRJNA1211679 | ENA

KAT6B overexpression rescues embryonic lethality in homozygous null KAT6A mice restoring vitality and normal lifespan.

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. Here we show that, surprisingly, 4-fold overexpression of Kat6b rescues all previously described developmental defects in Kat6a mutant mice, including rescuing the absence of hematopoietic stem cells. Kat6b restores acetylation at histone H3 lysines 9 and 23 and reverses critical gene expression anomalies in Kat6a mutant mice. Our data suggest that the target gene specificity of KAT6A can be substituted by the related paralogue KAT6B, despite differences in amino acid sequence, if KAT6B is expressed at sufficiently high levels.

| S-EPMC11861323 | biostudies-literature

Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363 [ATAC-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 | GSE233784 | GEO

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

2023-06-05 | GSE233783 | GEO

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

2023-06-05 | GSE233787 | 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

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

2023-06-05 | GSE233788 | GEO

RNA-seq profiling of mouse embryonic fibroblasts from Kat6a knockout and wildtype mice

Project description:Acetylation of histones by lysine acetyltransferases (KATs) is essential for transcriptional regulation of gene expression. The MYST family of KATs (KAT5-8) includes the oncogenes KAT6A (MOZ) and KAT6B (MORF/QKF). KAT6A has key roles in promoting cell proliferation through transcriptional activation of negative regulators of the Cdkn2a locus, which encode the tumor suppressors INK4A and ARF. To examine the loss of KAT6A function, mouse embryonic fibroblasts (MEFs) were isolated from E13.5 Kat6a+/+ and Kat6a–/– embryos and RNA-seq profiling was performed.

2018-08-03 | GSE108242 | GEO

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