PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation

Mol Cell. 2007 Mar 23;25(6):801-12. doi: 10.1016/j.molcel.2007.03.001. Epub 2007 Mar 15.


Posttranslational modification of chromatin by histone methylation has wide-ranging effects on nuclear function, including transcriptional regulation, maintenance of genome integrity, and epigenetic inheritance. The enzymes utilized to place histone methylation marks are well characterized, but the identity of a histone demethylation system remained elusive until recently. The discovery of histone demethylase enzymes capable of directly removing methyl groups from modified lysine residues has demonstrated that histone methylation is a dynamic modification. The most extensive family of histone demethylase enzymes identified so far contains a JmjC domain and catalyzes demethylation through a hydroxylation reaction. Here, we identify PLU-1, a transcriptional repressor implicated in breast cancer, as a histone demethylase enzyme that has the ability to reverse the trimethyl H3K4 modification state. Furthermore, we reveal that PLU-1-mediated H3K4 demethylase activity plays an important role in the proliferative capacity of breast cancer cells through repression of tumor suppressor genes, including BRCA1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Cycle
  • Cell Division
  • Cell Line, Tumor
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Jumonji Domain-Containing Histone Demethylases
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription, Genetic*


  • DNA-Binding Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • Jumonji Domain-Containing Histone Demethylases
  • KDM5B protein, human