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RNA-seq of murine proliferating neural stem and progenitor cells from Kat7-deleted mouse fetuses

ABSTRACT: Tissue-specific deletion of the gene encoding the histone acetyltransferase Kat7 (Hbo1) in the developing mouse central nervous system using cre-recombinase expression driven by regulatory sequences of the nestin locus (NesCre transgene) resulted in defective cerebral cortex development, a complete failure of neural stem cells to give rise to neurons and oligodendrocytes during in vitro differentiation, and a failure to express the neuronal differentiation program. Proliferating neural stem and progenitor cells (NPSCs) were isolated from Kat7-deleted and Kat7-intact 14.5 day embryonic mouse fetuses.

ORGANISM(S): Mus musculus

PROVIDER: GSE220498 | GEO | 2022/12/09

REPOSITORIES: GEO

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Chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq) detection of histone H3 lysine 14 acetylation (H3K14ac) and KAT7 (HBO1) in E14.5 mouse neural stem and progenitor cells (NSPCs)

Project description:Tissue specific deletion of the gene encoding the histone acetyltransferase KAT7 (HBO1) in the developing mouse central nervous system using cre-recombinase expression driven by regulatory sequences of the nestin locus (NesCre transgene) resulted in defective cerebral cortex development, a complete failure of neural stem cells to give rise to neurons and oligodendrocytes during in vitro differentiation and a failure to express the neuronal differentiation program. KAT7 genome occupancy and histone H3 lysine 14 acetylation (H3K14ac) levels were assessed by ChIP-seq in proliferating Kat7 deleted vs. Kat7 intact neural stem and progenitor cells (NSPCs). KAT7 and H3K14ac were completely absent in the Kat7 deleted cells. IN KAT7 intact cells, KAT7 occupancy levels and H3K14ac levels within the body of genes correlated strongly and positively. Both were higher in genes that were expressed strongly than in genes with lower or no expression. However, KAT7 and H3K14ac were present in all genes including silent genes and in all other regions of the genome, including intergenic regions and regions decorated with histone H3 lysine 9 trimethylation (H3K9me3), an indicator of constitutive heterochromatin.

2022-11-30 | GSE216459 | GEO

Stem cell plasticity, acetylation of H3K14 and de novo gene activation rely on KAT7

Project description:In the conventional model of transcriptional activation, transcription factors bind to response elements and recruit co-factors, including histone acetyltransferases. Contrary to this model, we show that the histone acetyltransferase KAT7 (HBO1/MYST2) is required genome-wide for histone H3 lysine 14 acetylation (H3K14ac). Examining neural stem cells, we found that KAT7 and H3K14ac were present not only at transcribed genes, but also at inactive genes, intergenic regions and in heterochromatin. KAT7 and H3K14ac were not required for the continued transcription of genes that were actively transcribed at the time of loss of KAT7, but indispensable for the activation of repressed genes. The absence of KAT7 abrogated neural stem cell plasticity, diverse differentiation pathways and cerebral cortex development. Reexpression of KAT7 restored stem cell developmental potential. Overexpression of KAT7 enhanced neuron and oligodendrocyte differentiation. Our data suggest that KAT7 prepares chromatin for transcriptional activation and is a prerequisite for gene activation.

2022-12-09 | GSE220602 | GEO

Effects of loss of the histone lysine acetyltransferase KAT7 on mRNA levels in proliferating and differentiating mouse neural stem cells (neurosphere cells) [RNA-seq]

Project description:RNA-seq data of neural stem and progenitor cell (NSPC) isolates from Kat7lox/loxNesCreT/+ and Kat7+/+NesCreT/+ E14.5 foetuses for each, proliferating and differentiating conditions. KAT7 and H3K14ac were not required for the continued transcription of genes that were actively transcribed at the time of loss of KAT7, but indispensable for the activation of repressed genes.

2022-11-30 | GSE215970 | GEO

The histone lysine acetyltransferase HBO1 (KAT7) regulates hematopoietic stem cell quiescence and self-renewal

Project description:In this study, we have used inducible and tissue-specific genetic deletion to investigate the function of HBO1 in the hematopoietic system. RNA-seq was used to examine the dependence of gene expression on the presence of HBO1(KAT7). Two different conditional expression sytems were used to induce Cre recombinase and delete a floxed allele of HBO1 in this study. This was to control for the treatement effect during Cre induction (interferon induction of Mx1-cre vs. tamoxifen induction of Rosa26-CreERT2). This data set indicates that HBO1 promotes expression of multiple genes encoding a hematopoietic transcription factor network essential for HSC quiescence and self-renewal in adult hematopoiesis.

2021-10-18 | GSE185959 | GEO

The histone acetyltransferase HBO1 (KAT7) promotes efficient tip cell sprouting during angiogenesis

Project description:Blood vessel growth and remodelling are essential during embryonic development and disease pathogenesis. The diversity of endothelial cells (ECs) is transcriptionally evident and ECs undergo dynamic changes in gene expression during vessel growth and remodelling.Here, we investigated the role of the histone acetyltransferase HBO1 (KAT7), which is important for activating genes during development and histone H3 lysine 14 acetylation (H3K14ac). Loss of HBO1 and H3K14ac impaired developmental sprouting angiogenesis and reduced pathological EC overgrowth in the retinal endothelium. Single-cell RNA-sequencing of retinal ECs revealed an increased abundance of tip cells in Hbo1 deleted retinas, which lead to EC overcrowding in the retinal sprouting front and prevented efficient tip cell migration. We found that H3K14ac was highly abundant in the endothelial genome in both intra- and intergenic regions suggesting that the role of HBO1 is as a genome organiser that promotes efficient tip cell behaviour necessary for sprouting angiogenesis.

2021-09-30 | GSE161310 | GEO

The histone acetyltransferase HBO1 (KAT7) promotes efficient tip cell sprouting during angiogenesis

2021-09-30 | GSE161236 | GEO

RNA-seq and ATAC-seq profiling of thymic epithelial cells from wildtype and Kat7 knockout mice

Project description:The autoimmune regulator, AIRE, induces the transcription of thousands of peripheral tissue genes (PTGs) in thymic epithelial cells (TECs) to mediate immunological tolerance. The chromatin state required for optimal AIRE function in TECs and how this state is induced remains unclear. Using RNA-seq and ATAC-seq, we tested the role of the histone acetyltransferase, KAT7 (also known as HBO1 or MYST2), which is essential for acetylation of histone 3 lysine 14 (H3K14), in TEC differentiation, AIRE-mediated PTG expression and thymic tolerance. We find that KAT7 is required for optimal expansion of medullary TEC and has a major role in the expression of AIRE-dependent PTGs, associated with enhanced chromatin accessibility at these gene loci in TECs. Mice with TEC-specific Kat7 deletion develop organ-specific autoimmunity with features resembling those observed in Aire-deficient mice. These findings highlight critical roles for KAT7-mediated acetylation in promoting a chromatin state at PTG loci that enables AIRE function and the establishment of immunological tolerance.

2021-12-21 | GSE188871 | GEO

The histone acetyltransferase HBO1 (KAT7) promotes efficient tip cell sprouting during angiogenesis

Project description:The histone acetyltransferase HBO1 (KAT7) promotes efficient tip cell sprouting during angiogenesis

| PRJNA676207 | ENA

The histone acetyltransferase HBO1 (KAT7) promotes efficient tip cell sprouting during angiogenesis

Project description:The histone acetyltransferase HBO1 (KAT7) promotes efficient tip cell sprouting during angiogenesis

| PRJNA675959 | ENA

A Genome-wide CRISPR-Based Screen Identifies KAT7 as a Senescence Driver

Project description:Understanding the genetic and epigenetic bases of cellular senescence is instrumental to aging intervention. We performed genome-wide CRISPR/Cas9-based screens in two human mesenchymal precursor cell (hMPC) models of progeroid syndromes and identified hundreds of genes whose deficiency alleviated cellular senescence. Among them, KAT7, a histone acetyltransferase, ranked as a top hit in both models. Inactivation of KAT7 decreased H3 lysine 14 acetylation (H3K14ac), repressed p15INK4b transcription, and rejuvenated both physiologically and pathologically aged cells. Moreover, lentiviral vectors encoding Cas9/sg-Kat7 alleviated liver senescence and extended healthspan and lifespan of mice. Our findings demonstrate that CRISPR/Cas9-based genetic screening is a robust method for systematically uncovering unknown senescence genes, of which KAT7 may represent a new therapeutic target for aging intervention.

2020-10-09 | GSE124197 | GEO

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