Beyond the histone tale: HP1α deregulation in breast cancer epigenetics

Cancer Biol Ther. 2015;16(2):189-200. doi: 10.1080/15384047.2014.1001277.

Abstract

Heterochromatin protein 1α (HP1α) encoded from the CBX5-gene is an evolutionary conserved protein that binds histone H3 di- or tri-methylated at position lysine 9 (H3K9me2/3), a hallmark for heterochromatin, and has an essential role in forming higher order chromatin structures. HP1α has diverse functions in heterochromatin formation, gene regulation, and mitotic progression, and forms complex networks of gene, RNA, and protein interactions. Emerging evidence has shown that HP1α serves a unique biological role in breast cancer related processes and in particular for epigenetic control mechanisms involved in aberrant cell proliferation and metastasis. However, how HP1α deregulation plays dual mechanistic functions for cancer cell proliferation and metastasis suppression and the underlying cellular mechanisms are not yet comprehensively described. In this paper we provide an overview of the role of HP1α as a new sight of epigenetics in proliferation and metastasis of human breast cancer. This highlights the importance of addressing HP1α in breast cancer diagnostics and therapeutics.

Keywords: CBX, chromobox homolog; CD, chromo domain; CSC, cancer stem cells; CSD, cromo shadow domain; CTE, C-terminal extension; DNMT, DNA-methyltransferase; EMT, epithelial-to-mesenchymal transition; HDMT, histone demethylase; HMT, histone methyltransferase; HP1, heterochromatin protein 1; NTE, N-terminal extension; PEV, position effect variegation; SOMU, sumoylation; TGS, transcriptional gene silencing; TSS, transcriptional start site; bp, base pair; breast-cancer, metastasis; chromatin; epigenetics; histone-modifications; invasion; mitosis; proliferation.

Publication types

  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Epigenesis, Genetic*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Histones / metabolism*
  • Humans
  • Multigene Family
  • Transcription, Genetic

Substances

  • CBX5 protein, human
  • Chromosomal Proteins, Non-Histone
  • Histones
  • Chromobox Protein Homolog 5