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Investigate the effect of loss of HAND2, MYCN, PHOX2B and GATA3 on chromatin accessibility.

ABSTRACT: The knockdown of HAND2 in IMR32 cells results in a decrease of chromation accessibility at the HAND2 and MYCN common binding sites.

ORGANISM(S): Homo sapiens

PROVIDER: GSE184229 | GEO | 2023/03/29

REPOSITORIES: GEO

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Investigate the effect of gain of HAND2 on chromatin accessibility.

Project description:The overexpression of HAND2 in IMR32 cells results in a increase of chromation accessibility at the HAND2 and MYCN common binding sites.

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RNA-sequencing analysis to investigate genes regulated by HAND2 and MYCN in IMR32 cells

Project description:In this study we identified genes regulated by HAND2 or MYCN or both MYCN and HAND2 in IMR32 cells.

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RNA-sequencing analysis to investigate genes regulated by HAND2 and MYCN in LAN5 cells

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Investigate the affect of CASZ1b on chromatin accessibility in SMS-CTR cells

Project description:In SMS-CTR cells, the overexpression of CASZ1b in SMS-CTR cells led to a modification of regional chromation accessibility.

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Dickkopf-1 is down-regulated by MYCN and inhibits neuroblastoma cell proliferation

Project description:Neuroblastomas are tumors of the developing peripheral sympathetic nervous system, which originates from the neural crest. Twenty percent of neuroblastomas show amplification of the MYCN oncogene, which correlates with poor prognosis. The MYCN transcription factor can activate and repress gene expression. To broaden our insight in the spectrum of genes down-regulated by MYCN, we generated gene expression profiles of the neuroblastoma cell lines SHEP-21N and SKNAS-NmycER, in which MYCN activity can be regulated. In this study, we show that MYCN suppresses the expression of Dickkopf-1 (DKK1) in both cell lines. DKK1 is a potent inhibitor of the wnt/beta-catenin signalling cascade, which is known to function in neural crest cell migration. We generated a DKK1 inducible cell line, IMR32-DKK1, which showed impaired proliferation upon DKK1 expression. Surprisingly, DKK1 expression did not inhibit the canonical wnt/beta-catenin signalling, suggesting a role of DKK1 in an alternative route of the wnt pathway. Gene expression profiling of two IMR32-DKK1 clones showed that only a few genes, amongst which SYNPO2, were up-regulated by DKK1. SYNPO2 encodes an actin-binding protein and was previously found to inhibit proliferation and invasiveness of prostate cancer cells. These results suggest that MYCN might stimulate cell proliferation by inhibiting the expression of DKK1. DKK1 might exert part of its growth suppressive effect by induction of SYNPO2 expression. Keywords: DKK1, MYCN, neuroblastoma, Dickkopf

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Hand2 selectively reorganizes chromatin accessibility to induce pacemaker-like transcriptional reprogramming (ATAC-seq)

Project description:Gata4, Mef2c, Hand2, and Tbx5 (GHMT) can reprogram transduced fibroblasts into induced pacemaker-like myocytes (iPMs), but the underlying mechanisms remain obscure. Here we explored the role of Hand2 in iPM formation by using a combination of transcriptome, genome, and biochemical assays. We found many shared transcriptional signatures between iPMs and endogenous sinoatrial node (SAN), yet key regulatory networks remain missing. We demonstrate that Hand2 augments chromatin accessibility at loci involved in sarcomere organization, electrical coupling, and membrane depolarization. Focusing on an established cardiac Hand2 cistrome, we observe selective reorganization of chromatin accessibility to promote pacemaker-specific gene expression. Moreover, we identify a novel Hand2 cardiac subtype diversity (CSD) domain through biochemical analysis of the N-terminus. By integrating our RNA-seq and ATAC-seq datasets, we highlight desmosome organization as a hallmark feature of iPM formation. Collectively, our results illuminate Hand2-dependent mechanisms that may guide future efforts to rationally improve iPM formation.

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