LSD1 is required for chromosome segregation during mitosis

Eur J Cell Biol. 2010 Jul;89(7):557-63. doi: 10.1016/j.ejcb.2010.01.004. Epub 2010 Feb 26.

Abstract

Dynamic methylation/demethylation of histones and non-histone proteins occurs during the cell cycle. Lysine-specific demethylase 1 (LSD1) exhibits diverse transcriptional activities through catalyzing demethylation of mono- and di-methylated histone H3 on lysine 4 (H3K4) and lysine 9 (H3K9). We show here that inhibition of LSD1 expression by siRNA leads to abnormal chromosomal segregation in unperturbed mitosis and abnormal centrosome duplication, and is associated with decreased protein levels of MAD2 and BUBR1. LSD1 positively regulates the BUBR1 and MAD2 promoter activity and maintains local monomethylation status of H3K9, which is a repressive histone mark for gene transcription. Expression of exogenous BUBR1 and MAD2 in LSD1-depleted cells partially rescues the defect of chromosome segregation. Our results suggest that LSD1 plays a role in chromosomal segregation during mitosis partially through transcriptional regulation of BUBR1 and MAD2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Binding Proteins / genetics
  • Cell Cycle Proteins / genetics
  • Centrosome / metabolism
  • Chromatin Immunoprecipitation
  • Chromosome Segregation / genetics
  • Chromosome Segregation / physiology*
  • HeLa Cells
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism*
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Mad2 Proteins
  • Mitosis / genetics
  • Mitosis / physiology*
  • Promoter Regions, Genetic / genetics
  • Protein-Serine-Threonine Kinases / genetics
  • Repressor Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • MAD2L1 protein, human
  • Mad2 Proteins
  • Repressor Proteins
  • Histone Demethylases
  • KDM1A protein, human
  • BUB1 protein, human
  • Bub1 spindle checkpoint protein
  • Protein-Serine-Threonine Kinases