Molecular Therapy: Nucleic Acids (Dec 2024)

CHD6 eviction of promoter nucleosomes maintains housekeeping transcriptional program in prostate cancer

  • Lina Bu,
  • Shaodong Huang,
  • Ziyan Rao,
  • Chenyang Wu,
  • Bryan-Yu Sun,
  • Yanhua Liu,
  • Lin He,
  • Dongyu Zhao

Journal volume & issue
Vol. 35, no. 4
p. 102397

Abstract

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CHD6, a member of the chromodomain helicase DNA-binding protein family, has been implicated in various diseases and tumors. However, its precise binding model of CHD6 on regulatory functional genes remains poorly understood. In this study, we discovered sharp peaks of CHD6, as the first member of CHD family for housekeeping process, binding only to the promoter region of genes in the C4-2 cell line. These genes, with conserved sharp CHD6 peaks across tumor cells, likely represent housekeeping genes ADNP and GOLGA5. Genes with sharp CHD6 peaks exhibit stable and low expression levels, sharing epigenetic features similar to housekeeping genes. Furthermore, this regulatory model also exists in both HEK293 cells and cardiomyocytes. Overall, the results of this study demonstrate that CHD6 binds to the promoter regions of housekeeping genes, regulating their histone modifications, chromatin structure, and gene expression.

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