Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Deficiency of Autism Risk Factor Ash1l in Prefrontal Cortex Induces Genetic Aberrations, Synaptic Imbalance and Severe Seizures

ABSTRACT: We performed RNAseq experiments to examine genome-wide transcriptional changes in PFC of shRNA-ASH1L KD mice compared to GFP injected control mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE181819 | GEO | 2021/08/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Deficiency of Autism Risk Factor Ash1l in Prefrontal Cortex Induces Genetic Aberrations, Synaptic Imbalance and Severe Seizures

Project description:Deficiency of Autism Risk Factor Ash1l in Prefrontal Cortex Induces Genetic Aberrations, Synaptic Imbalance and Severe Seizures

| PRJNA753521 | ENA

Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures

Project description: Not available

| S-EPMC8593046 | biostudies-literature

ASH1L links histone H3 lysine 36 di-methylation to leukemia

Project description:The histone methyltransferases MLL and ASH1L are trithorax-group proteins that interact genetically through undefined molecular mechanisms to regulate developmental and hematopoietic gene expression. Here we show that the lysine 36-dimethyl mark of histone H3 (H3K36me2) written by ASH1L is preferentially bound in vivo by LEDGF, an MLL-associated protein that co-localizes with MLL, ASH1L and H3K36me2 on chromatin genome wide. Furthermore, ASH1L facilitates recruitment of LEDGF and wild type MLL proteins to chromatin at key leukemia target genes, and is a crucial regulator of MLL-dependent transcription and leukemic transformation. Conversely KDM2A, an H3K36me2 demethylase and Polycomb-group silencing protein, antagonizes MLL-associated leukemogenesis. Our studies illuminate the molecular mechanisms underlying epigenetic interactions wherein placement, interpretation and removal of H3K36me2 contribute to the regulation of gene expression and MLL leukemia, and suggest ASH1L as a target for therapeutic intervention. Investigation of multiple transcription factors and histone modification marks in MV4-11 human leukemia cells.

2016-07-01 | E-GEOD-73528 | biostudies-arrayexpress

Histone H3K36me2-specific methyltransferase ASH1L promotes the MLL-AF9-induced leukemogenesis

Project description:ASH1L and MLL1 are two histone methyltransferases that facilitate transcriptional activation during normal development. However, the roles of ASH1L and its enzymatic activity in the development of MLL-rearranged leukemias are not fully elucidated in Ash1L gene knockout animal models. In this study, we used an Ash1L conditional knockout mouse model to show that loss of ASH1L in hematopoietic progenitor cells impaired the initiation of MLL-AF9-induced leukemic transformation in vitro. Furthermore, genetic deletion of ASH1L in the MLL-AF9-transformed cells impaired the maintenance of leukemic cells in vitro and largely blocked the leukemia progression in vivo. Importantly, the loss of ASH1L function in the Ash1L-deleted cells could be rescued by wild-type but not the catalytic-dead mutant ASH1L, suggesting the enzymatic activity of ASH1L was required for its function in promoting MLL-AF9-induced leukemic transformation. At the molecular level, ASH1L enhanced the MLL-AF9 target gene expression by directly binding to the gene promoters and modifying the local histone H3K36me2 levels. Thus, our study revealed the critical functions of ASH1L in promoting the MLL-AF9-induced leukemogenesis, which provides a molecular basis for targeting ASH1L and its enzymatic activity to treat MLL-arranged leukemias.

2021-09-07 | GSE183413 | GEO

ASH1L methyltransferase deposits H3K4me3 and FACT for damage verification in nucleotide excision repair [ChIP-Seq ASH1L-CTD]

Project description:To recognize DNA damage, nucleotide excision repair (NER) deploys a multipart mechanism by which the XPC sensor detects helical distortions followed by engagement of TFIIH for lesion verification. Accessory players ensure that this factor handover takes place on chromatin where DNA is wrapped around histones. We show that the histone methyltransferase ASH1L, once activated by MRG15, accelerates global-genome NER activity. Upon UV irradiation, ASH1L deposits H3K4me3 marks all over the genome (except in gene promoters), thus priming chromatin for relocations of XPC from native to damaged DNA. ASH1L further recruits the histone chaperone FACT to UV lesions. In the absence of ASH1L, MRG15 or FACT, XPC persists on damaged DNA without being able to deliver lesions to the TFIIH verifier. We conclude that ASH1L implements repair hotspots whose H3K4me3 and FACT occupancy confers an active promoter-like code and organization of histones that make DNA damage verifiable by the NER machinery.

2023-06-08 | GSE227008 | GEO

Autism risk gene KMT5B deficiency in prefrontal cortex induces synaptic dysfunction and social deficits via alterations of DNA repair and gene transcription

Project description:We performed RNAseq experiments to examine genome-wide transcriptional changes in PFC of shRNA-Kmt5b KD mice compared to GFP injected control mice.

2021-08-12 | GSE181807 | GEO

Structure-function relationship of ASH1L and histone H3K36 and H3K4 methylation

Project description:The ASH1L lysine methyltransferase plays a critical role in development and is frequently dysregulated in cancer and neurodevelopmental diseases. ASH1L catalyzes mono- and dimethylation of histone H3K36 and contains a set of uncharacterized domains. Here, we report the structure-function relationships of the C-terminal cassette of ASH1L encompassing a bromodomain (BD), a PHD finger and a bromo-associated homology (BAH) domain and show that ASH1L co-localizes with H3K4me3 but not with H3K36me2 at transcription start sites genome-wide and is involved in embryonic stem cell differentiation and transcriptional regulation of differentiation marker genes. Our crystal and NMR structural data provide mechanistic details for the recognition of H3K4me3 by PHD, the DNA binding activities of BD and BAH, and crosstalk among these domains. We show that the PHD-H3K4me3 interaction is inhibitory to the catalytic activity of ASH1L and that the DNA binding function of BAH is necessary for ASH1L engagement with the nucleosome. Our findings suggest a mechanism by which the C-terminus of ASH1L associates with chromatin and provide molecular and structural insights that are essential in therapeutic targeting of ASH1L.

2023-04-23 | GSE199438 | GEO

ASH1L links histone H3 lysine 36 di-methylation to leukemia

2016-07-01 | GSE73528 | GEO

Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors

Project description:Autism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causality and underlying molecular mechanisms linking ASH1L mutations to genesis of ASD/ID remains undetermined. Here we show loss of ASH1L in the developing mouse brain is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. Gene expression analyses uncover critical roles of ASH1L in regulating gene expression during neural cell development. Thus, our study establishes a new ASD/ID mouse model revealing the critical function of an epigenetic factor ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities.

2021-05-23 | GSE173262 | GEO

Genome-wide distribution of ASH1L and H3K36me2 in human MV4;11 leukemia cell line

Project description:The H3K36me2 and ASH1L levels are compared in the presence or absence of the inhibitor of the ASH1L activity.

2021-02-24 | GSE150086 | GEO