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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 21, 2022 |
| Title |
The histone variant macroH2A modulates inflammatory response in cancer [UMI-4C] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
MacroH2A histone variants have a major role in nuclear organization and large-scale 3D chromatin architecture. How these alterations impinge on the behaviour of cancer cells is not known. Here, we describe the analysis of the total macroH2A loss of function phenotype in a model of hepatoblastoma, the main childhood liver cancer. Performing transcriptomic analyses in xenografts and cell cultures, we find that macroH2A modulated the response of cancer cells to paracrine inflammatory signalling. Specifically, ablation of macroH2A ablation neutralized the induction of a large subset of genes by TNFα and led to the hyperactivation of another subset of genes. Among the top macroH2A-sensitive genes we find the cancer-related gene DKK1 . Depletion of macroH2A rendered the DKK1 gene hypersensitive to TNFα signalling boosting the secretion of DKK1 protein. On the gene regulation level, this was mediated by an alteration of the local chromatin structure and facilitated activation of distal enhancer elements. The study of human samples of hepatoblastoma showed that DKK1 is strongly upregulated in tumors and associated with poor patient outcome. Taken together our results suggest that the regulation of 3D chromatin architecture by macroH2A histone variants has a central role in the response and regulation of paracrine signalling that might be relevant for the interaction of cancers with immune cells and other cells in their microenvironment.
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| Overall design |
UMI-4C assays performed in HepG2 cell lines stably expressing either control shRNAs (CTL) or shRNAs targeting macroH2A1 and macroH2A2 (DKD)
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| Contributor(s) |
Corujo D, Malinverni R, Buschbeck M |
| Citation(s) |
35732123 |
| Submission date |
May 20, 2022 |
| Last update date |
Sep 20, 2022 |
| Contact name |
Roberto Malinverni |
| E-mail(s) |
rmalinverni@carrerasresearch.org
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| Organization name |
Josep Carreras Leukaemia Research Institute
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| Street address |
Josep Carreras Building, Ctra de Can Ruti,
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| City |
Badalona |
| State/province |
Barcelona |
| ZIP/Postal code |
08916 |
| Country |
Spain |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (19)
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| GSM6172816 |
CTL, rep4, MBL2 |
| GSM6172817 |
DKD, rep1, MBL2 |
| GSM6172818 |
DKD, rep2, MBL2 |
| GSM6172819 |
DKD, rep3, MBL2 |
| GSM6172820 |
DKD, rep4, MBL2 |
| GSM6172821 |
CTL, rep1, EREG, L1 |
| GSM6172822 |
CTL, rep2, EREG, L1 |
| GSM6172823 |
CTL, rep3, EREG, L1 |
| GSM6172824 |
DKD, rep1, EREG, L1 |
| GSM6172825 |
DKD, rep2, EREG, L1 |
| GSM6172826 |
CTL, rep1, EREG, L2 |
| GSM6172827 |
CTL, rep2, EREG, L2 |
| GSM6172828 |
CTL, rep3, EREG, L2 |
| GSM6172829 |
DKD, rep1, EREG, L2 |
| GSM6172830 |
DKD, rep2, EREG, L2 |
| GSM6172831 |
DKD, rep3, EREG |
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| This SubSeries is part of SuperSeries: |
| GSE161859 |
The histone variant macroH2A modulates inflammatory response in cancer |
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| Relations |
| BioProject |
PRJNA840922 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE203475_RAW.tar |
5.5 Mb |
(http)(custom) |
TAR (of TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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