Transcription factors RUNX1/AML1 and RUNX2/Cbfa1 dynamically associate with stationary subnuclear domains

Kimberly S. Harrington, Amjad Javed, Hicham Drissi, Sandra McNeil, Jane B. Lian, Janet L. Stein, André J. van Wijnen, Yu Li Wang, Gary S. Stein

Research output: Contribution to journalReview articlepeer-review

72 Scopus citations

Abstract

The runt-related transcription factors (RUNX/Cbfa/AML) are essential for cellular differentiation and fetal development. C-terminal truncations of RUNX factors that eliminate the targeting of these factors to subnuclear foci result in lethal hematopoietic and skeletal phenotypes. Here we demonstrate that in living cells the RUNX C-terminus is necessary for the dynamic association of RUNX into stable subnuclear domains. Time-lapse fluorescence microscopy shows that RUNX1 and RUNX2 localize to punctate foci that remain stationary in the nuclear space. By fluorescence recovery after photobleaching assays, both proteins are shown to dynamically associate at these subnuclear foci, with a 10 second half-time of recovery. A truncation of RUNX2, removing its intranuclear targeting signal (NMTS), increases its mobility by an order of magnitude, resulting in a half-time of recovery equivalent to that of EGFP alone. We propose that the dynamic shuttling of RUNX factors in living cells to positionally stabilized foci, which is dependent on the C-terminus, is a component of the mechanism for gene regulation in vivo.

Original languageEnglish (US)
Pages (from-to)4167-4176
Number of pages10
JournalJournal of cell science
Volume115
Issue number21
DOIs
StatePublished - Nov 1 2002

Keywords

  • Fluorescence recovery after photobleaching
  • Green fluorescent protein
  • Intranuclear targeting
  • Nuclear matrix
  • Runt homology factors

ASJC Scopus subject areas

  • Cell Biology

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