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Heterochromatin spreading in cancer cells through HDAC7 mediated histone H3.3 landscape reprogramming [RNA-seq]

GSE286177 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2026/01/07 Platform GPL16791
Summary
Class IIa histone deacetylases (HDACs) are a family of enzymes that despite their name, do not have any measurable histone deacetylase activity but they function as multi-protein interaction hubs due to the presence of a prolonged N-terminal domain. Here we show that HDAC7, a member of the Class IIa HDAC family, is a chaperone for Histone H3.3 and, interacts with H3.3 and HIRA on chromatin. Specific inhibition of HDAC7 expression with subtype specific siRNAs results in inhibition of the interaction of H3.3 with HIRA, while the association of H3.3 with DAXX and H3K9me3 is significantly increased, resulting in H3.3 being deposited on H3K9me3+/DAPI+ heterochromatin nuclear foci with observed changes in RNA expression. This drives substantial alteration of cancer cell gene expression as well as inhibition of the stemness phenotype for cancer cells. To understand the genome wide effect on expression, we perform RNA-seq following HDAC7 knockdown.
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Also filed as BioProject PRJNA1208069 and SRA study SRP556138. Searching any of these in the dataset finder brings you back here.

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