Gene-specific factors determine mitotic expression and bookmarking via alternate regulatory elements

Nucleic Acids Res. 2013 Feb 1;41(4):2202-15. doi: 10.1093/nar/gks1365. Epub 2013 Jan 8.


Transcriptional silencing during mitosis is caused by inactivation of critical transcriptional regulators and/or chromatin condensation. Inheritance of gene expression patterns through cell division involves various bookmarking mechanisms. In this report, we have examined the mitotic and post-mitotic expression of the DRA major histocompatibility class II (MHCII) gene in different cell types. During mitosis the constitutively MHCII-expressing B lymphoblastoid cells showed sustained occupancy of the proximal promoter by the cognate enhanceosome and general transcription factors. In contrast, although mitotic epithelial cells were depleted of these proteins irrespectively of their MHCII transcriptional activity, a distal enhancer selectively recruited the PP2A phosphatase via NFY and maintained chromatin accessibility. Based on our data, we propose a novel chromatin anti-condensation role for this element in mitotic bookmarking and timing of post-mitotic transcriptional reactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCAAT-Binding Factor / metabolism
  • Cell Cycle / genetics
  • Cell Line
  • Chromatin / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • DNA-Binding Proteins / metabolism
  • Enhancer Elements, Genetic
  • G1 Phase / genetics
  • Gene Expression Regulation
  • HLA-DR alpha-Chains / genetics*
  • Humans
  • Locus Control Region
  • Mitosis / genetics*
  • Promoter Regions, Genetic
  • Protein Phosphatase 2 / metabolism
  • Regulatory Factor X Transcription Factors
  • Transcription, Genetic*


  • CCAAT-Binding Factor
  • Chromatin
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • HLA-DR alpha-Chains
  • NFYA protein, human
  • RFX5 protein, human
  • Regulatory Factor X Transcription Factors
  • Protein Phosphatase 2