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Promoter and enhancer RNAs regulate chromatin reorganization and activation of miR-10b/HOXD locus and neoplastic transformation in glioma [ChIP-seq]

ABSTRACT: Promoter and enhancer RNAs regulate chromatin reorganization and activation of miR-10b/HOXD locus and neoplastic transformation in glioma [ChIP-seq]

PROVIDER: PRJNA676095 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15838217.fastq.gz	Fastqsanger.gz
	SRR15838218.fastq.gz	Fastqsanger.gz
	SRR15838219.fastq.gz	Fastqsanger.gz
	SRR15838220.fastq.gz	Fastqsanger.gz
	SRR15838221.fastq.gz	Fastqsanger.gz

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Promoter and enhancer RNAs regulate chromatin reorganization and activation of miR-10b/HOXD locus and neoplastic transformation in glioma [ChIP-seq]

Project description:Using a combination of chromatin capture techniques, ChIP-Seq, single-molecule in situ RNA analysis, and computational analysis of large-scale TCGA datasets, we identified an epigenetic mechanism underlying common activation of HOXD/miR-10b locus in otherwise highly heterogenous glioma brain tumors. We demonstrate for the first time that two remote lncRNAs, one associated with a genomic promoter and another with a newly identified enhancer, cooperatively shape the 3D chromatin structure and looping, leading to the activation of a large gene cluster (12 genes, 110 KB) that includes the regulatory miRNA essential for glioma survival. This work describes a new mechanism contributing to neoplastic transformation in gliomagenesis, and identifies new avenues for therapeutic interventions based on the promoter and enhancer associated regulatory transcripts.

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Promoter and enhancer RNAs regulate chromatin reorganization and activation of miR-10b/HOXD locus and neoplastic transformation in glioma

Project description:Promoter and enhancer RNAs regulate chromatin reorganization and activation of miR-10b/HOXD locus and neoplastic transformation in glioma

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Promoter and enhancer RNAs regulate chromatin reorganization and activation of miR-10b/HOXD locus and neoplastic transformation in glioma [4C-seq]

Project description:Promoter and enhancer RNAs regulate chromatin reorganization and activation of miR-10b/HOXD locus and neoplastic transformation in glioma [4C-seq]

| PRJNA676096 | ENA

Promoter and enhancer RNAs regulate chromatin reorganization and activation of miR-10b/HOXD locus, and neoplastic transformation in glioma.

Project description:miR-10b is silenced in normal neuroglial cells of the brain but commonly activated in glioma, where it assumes an essential tumor-promoting role. We demonstrate that the entire miR-10b-hosting HOXD locus is activated in glioma via the cis-acting mechanism involving 3D chromatin reorganization and CTCF-cohesin-mediated looping. This mechanism requires two interacting lncRNAs, HOXD-AS2 and LINC01116, one associated with HOXD3/HOXD4/miR-10b promoter and another with the remote enhancer. Knockdown of either lncRNA in glioma cells alters CTCF and cohesin binding, abolishes chromatin looping, inhibits the expression of all genes within HOXD locus, and leads to glioma cell death. Conversely, in cortical astrocytes, enhancer activation is sufficient for HOXD/miR-10b locus reorganization, gene derepression, and neoplastic cell transformation. LINC01116 RNA is essential for this process. Our results demonstrate the interplay of two lncRNAs in the chromatin folding and concordant regulation of miR-10b and multiple HOXD genes normally silenced in astrocytes and triggering the neoplastic glial transformation.

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Promoter and enhancer RNAs regulate chromatin reorganization and activation of miR-10b/HOXD locus and neoplastic transformation in glioma

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-11-11 | GSE161258 | GEO

Reorganization of HoxD regulatory landscapes during the evolution of a snake-like body plan (ChIP-seq)

Project description:While the vertebrate body plan is highly conserved amongst all species of this taxon, extreme variations thereof can be documented in snakes, which display both an absence of limbs and an unusually elongated trunk. As Hox genes are strong candidates both for the making and the evolution of this body plan, their comparative study in such a morphologically diverged group is informative regarding their potential causative importance in these processes. In this work we use an interspecies comparative approach where different aspects of regulation at the HoxD locus are investigated. We find that although spatial collinearity and associated epigenetic mark dynamics are conserved in the corn snake, other regulatory modalities have been largely restructured. A BAC transgenic approach indeed revealed that, while the majority of mesodermal enhancers in vertebrates appear to be mostly located outside of the cluster, the corn snake contains most mesodermal trunk enhancers within the HoxD cluster. We also find that, despite the absence of limbs and an altered Hoxd gene regulation in external genitalia, the bimodal chromatin structure at the corn snake HoxD locus is maintained. The analysis of particular enhancer sequences initially defined in the mouse and further isolated at the snake orthologous locus showed differences in their specificities for the limb and genital bud expression. Of particular interest, a snake counterpart of a mouse limb-only enhancer sequence evolved into a genital-only enhancer. Such a regulatory exaptation suggests that enhancer versatility may have been an important factor to accompany the transition towards the snake body plan. These results show that vertebrate morphological evolution is likely to have been associated with extensive reorganization at the HoxD regulatory landscapes while respecting a very conserved general regulatory framework.

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