Inhibition of HDAC7 reprograms the histone H3.3 landscape to induce heterochromatin spreading and DNA replication defects in cancer cells.

ABSTRACT: Class IIa histone deacetylases (HDACs) have minimal HDAC activity but may function as multiprotein interaction hubs. Here, we demonstrated the expression of histone deacetylase 7 (HDAC7), a class IIa HDAC family member, in glioblastoma tumor tissue from 84 patients, patient-derived glioma stem cells from six patients, and pediatric diffuse pontine glioma cells from three patients. HDAC7 binds to histone H3.3 and interacts with H3.3 and HIRA on chromatin. Targeted downregulation of HDAC7 expression with a subtype-specific siRNA inhibits the interaction of H3.3 with HIRA, increasing the association of H3.3 with DAXX and histone lysine trimethylation at lysine 9 (H3K9me3), leading to H3.3 deposition on H3K9me3⁺/4',6-diamidino-2-phenylindole⁺ heterochromatin nuclear foci.

SUBMITTER: Hassan O 

PROVIDER: S-EPMC12547473 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature