Live cell imaging of the cancer-related transcription factor RUNX2 during mitotic progression
Authors
Pockwinse, Shirwin M.Kota, Krishna P.
Quaresma, Alexandre J. C.
Imbalzano, Anthony N.
Lian, Jane B.
Van Wijnen, Andre J.
Stein, Janet L.
Stein, Gary S.
Nickerson, Jeffrey A.
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2011-05-01
Metadata
Show full item recordAbstract
The nuclear matrix bound transcription factor RUNX2 is a lineage-specific developmental regulator that is linked to cancer. We have previously shown that RUNX2 controls transcription of both RNA polymerase II genes and RNA polymerase I dependent ribosomal RNA genes. RUNX2 is epigenetically retained through mitosis on both classes of target genes in condensed chromosomes. We have used fluorescence recovery after photobleaching (FRAP) to measure the relative binding kinetics of EGFP-RUNX2 at transcription sites in the nucleus and nucleoli during interphase, as well as on mitotic chromosomes. RUNX2 becomes more strongly bound as cells go from interphase through prophase, with a doubling of the most tightly bound "immobile fraction". RUNX2 exchange then becomes much more facile during metaphase to telophase. During interphase the less tightly bound pool of RUNX2 exchanges more slowly at nucleoli than at subnuclear foci, and the non-exchanging immobile fraction is greater in nucleoli. These results are consistent with a model in which the molecular mechanism of RUNX2 binding is different at protein-coding and ribosomal RNA genes. The binding interactions of RUNX2 change as cells go through mitosis, with binding affinity increasing as chromosomes condense and then decreasing through subsequent mitotic phases. The increased residence of RUNX2 at mitotic chromosomes may reflect its epigenetic function in "bookmarking" of target genes in cancer cells. (c) 2010 Wiley-Liss, Inc.Source
J Cell Physiol. 2011 May;226(5):1383-9. doi: 10.1002/jcp.22465. Epub 2010 Oct 13. Link to article on publisher's siteDOI
10.1002/jcp.22465Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49610PubMed ID
20945391Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1002/jcp.22465