Two opposing gene expression patterns within ATRX aberrant neuroblastoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA941435 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23719400_1.fastq.gz | Fastqsanger.gz | |||
| SRR23719400_2.fastq.gz | Fastqsanger.gz | |||
| SRR23719401_1.fastq.gz | Fastqsanger.gz | |||
| SRR23719401_2.fastq.gz | Fastqsanger.gz | |||
| SRR23719402_1.fastq.gz | Fastqsanger.gz |
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Project description:Here, we report that ATRX co-localizes with the H3K9-methyl transferase SETDB1 (also known as ESET), the co-repressor TRIM28 (also known as KAP1), and the transcription factor ZNF274 at 3â exons of Zinc Finger Genes (ZNFs) containing an atypical H3K9me3/H3K36me3 chromatin signature. Disruption of ATRX and ZNF274 leads to a significant reduction of H3K9me3, particularly at the 3â ZNF exons and other atypical chromatin regions, higher percentages of DNA damage, and defects in cell cycle. Taken together, our studies suggest that ATRX binds the 3â exons of ZNFs to maintain genomic stability through the regulation of their H3K9me3 levels XL-MNase ChIP-seq of ATRX was performed in the erythroleukemic cell line K562 and the Neuroblastoma cell line LAN6. Two independent replicates using different ATRX antibodies were performed in K562. Additionally, Native ChIP-seq of H3K9me3 in LAN6, ATRX WT and ATRX KO K562 cells was performed. Input samples were sequenced as control.
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Project description:Alterations in the tumor suppressor ATRX are recurrently observed in several cancer types including sarcomas, which are mesenchymal neoplasms. ATRX has multiple epigenetic functions including heterochromatin formation and maintenance and regulation of transcription through modulation of chromatin accessibility. Here, we show in murine mesenchymal progenitor cells (MPCs) that Atrx deficiency aberrantly activated mesenchymal differentiation programs. This includes adipogenic pathways where ATRX loss induced expression of adipogenic transcription factors (Pparγ and Cebpα) and enhanced adipogenic differentiation in response to differentiation stimuli. These changes are linked to loss of heterochromatin near mesenchymal lineage genes together with increased chromatin accessibility and gains of active chromatin marks at putative enhancer elements and promoters. Finally, we observed depletion of H3K9me3 at transposable elements, which are derepressed including near mesenchymal genes where they could serve as regulatory elements. Our results demonstrate ATRX functions to buffer against differentiation in mesenchymal progenitor cells, which has implications for understanding ATRX loss of function in sarcomas.
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