Mechanism of hsp70i gene bookmarking.
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.
Xing
Hongyan
H
Department of Molecular and Cellular Biochemistry, Chandler Medical Center, University of Kentucky, Lexington, KY 40536, USA.
Wilkerson
Donald C
DC
Mayhew
Christopher N
CN
Lubert
Eric J
EJ
Skaggs
Hollie S
HS
Goodson
Michael L
ML
Hong
Yiling
Y
Park-Sarge
Ok-Kyong
OK
Sarge
Kevin D
KD
D000251:Adenosine Triphosphatases / Q000378:metabolism; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D047468:Immunoprecipitation; D007399:Interphase; D008938:Mitosis; D046912:Multiprotein Complexes; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054648:Protein Phosphatase 2; D021122:Protein Subunits / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D046912:Multiprotein Complexes; D021122:Protein Subunits; D034741:RNA, Small Interfering; D014157:Transcription Factors; C108312:condensin complexes; C070389:HSF2 protein, human; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D000251:Adenosine Triphosphatases