Journal: Cell Reports Medicine
Article Title: Histone lysine demethylase 4 family proteins maintain the transcriptional program and adrenergic cellular state of MYCN-amplified neuroblastoma
doi: 10.1016/j.xcrm.2024.101468
Figure Lengend Snippet: QC6352 impacts the chromatin accessibility of ADRN CRC TFs in MYCN -amplified cells (A and B) Adrenergic or mesenchymal median score in response to DMSO or 100 nM of QC6352 treatment for 48 h in adrenergic dominant cell lines (BE2C, SIMA, and KELLY) (A) and mesenchymal dominant cell lines (SK-N-AS and SK-N-SH) (B). KDM4 inhibition results in enhanced MES scoring with reduced ADRN signatures in all tested cell lines (red arrow indicates direction of signature change). (C) HOMER Motif analysis showing the predicted adrenergic CRC TF binding motifs in which genome-wide chromatin accessibility is impacted by QC6352 treatment of SIMA cells. (D) PHOX2A, ASCL1, and MYCN motif densities around ATAC-seq open chromatin regions (±1,000 bp) by categories in SIMA cells. Motif density was determined by the HOMER program and normalized to that in a background sequence of equal length. (E) STRING network analysis of transcriptional factors predicted to bind the regions with reduced chromatin accessibility by QC6352 treatment of SIMA cells. The expression threshold for genes encoding TFs is set as log2CPM > 1. CPM, counts per million mapped reads. Red color indicates ADRN CRC TFs. Blue color indicates MES CRC TFs. (F) IGV snapshots show chromatin accessibility at MYCN , HAND2 , PHOX2B , and ALK loci is reduced by QC6352 in SIMA and BE2C cells. (G) Density heatmaps for CUT&TAG of KDM4A-C genomic binding in BE2C cells, and ChIP-seq density heatmaps of the indicated histone marks in BE2C cells after 48 h treatment with control or 200 nM QC6352, ranked by MYCN read intensity within ± 5 kb of peak summits. MYCN ChIP-seq data were retrieved from GEO SuperSeries GSE94824. (H) The indicated epigenetic marks upregulated and downregulated by QC6352 treatment of BE2C cells for 48 h followed by ChIP-seq or CUT&TAG analyses. (I) The global distribution of H3K9me3, H3K36me3, H3K27Ac, H3K4me1, and H3K27me3 peaks at different regions of annotated genes. 3′ UTR, 3′ untranslated region; 5′ UTR, 5′ untranslated region; TSS, transcription start site. (J) Snapshot of using the IGV program displaying the KDM4s, H3K9me3, H3K36me3, H3K27me3, H3K27Ac, and H3K4me1 peaks at the PHOX2B and ASCL1 genomic loci.
Article Snippet: HAND2 (dHAND) , Santa Cruz , sc-398167, NA.
Techniques: Amplification, Inhibition, Binding Assay, Genome Wide, Sequencing, Expressing, ChIP-sequencing, Control
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