Mechanism of hsp70i Gene Bookmarking

Xing, Hongyan
Wilkerson, Donald C.
Mayhew, Christopher N.
Lubert, Eric J.
Skaggs, Hollie S.
Goodson, Michael L.
Hong, Yiling
Park-Sarge, Ok-Kyong
Sarge, Kevin D.

¹Department of Molecular and Cellular Biochemistry, ²Department of Physiology, Chandler Medical Center, University of Kentucky, Lexington, KY 40536, USA. ³Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati, Cincinnati, OH 45267, USA. ⁴Battelle Memorial Institute, Columbus, OH 43201, USA. ⁵Section of Microbiology, University of California at Davis, Davis, CA 95616, USA.

*To whom correspondence should be addressed. E-mail: [email protected]

Supporting Online Material: www.sciencemag.org/cgi/content/full/307/5708/421/DC1; Materials and Methods; Figs. S1 to S3; References and Notes

18 October 2004; accepted 24 November 2004

10.1126/science.1106478

Science 307(5708):p 421-423, January 21, 2005.

In contrast to most genomic DNA in mitotic cells, the promoter regions of some genes, such as the stress-inducible hsp70i gene that codes for a heat shock protein, remain uncompacted, a phenomenon called bookmarking. Here we show that hsp70i bookmarking is mediated by a transcription factor called HSF2, which binds this promoter in mitotic cells, recruits protein phosphatase 2A, and interacts with the CAP-G subunit of the condensin enzyme to promote efficient dephosphorylation and inactivation of condensin complexes in the vicinity, thereby preventing compaction at this site. Blocking HSF2-mediated bookmarking by HSF2 RNA interference decreases hsp70i induction and survival of stressed cells in the G₁ phase, which demonstrates the biological importance of gene bookmarking.