Abstract
Multiple enzymatic activities are required for transcriptional initiation. The enzyme DNA topoisomerase II associates with gene promoter regions and can generate breaks in double-stranded DNA (dsDNA). Therefore, it is of interest to know whether this enzyme is critical for regulated gene activation. We report that the signal-dependent activation of gene transcription by nuclear receptors and other classes of DNA binding transcription factors, including activating protein 1, requires DNA topoisomerase IIbeta-dependent, transient, site-specific dsDNA break formation. Subsequent to the break, poly(adenosine diphosphate-ribose) polymerase-1 enzymatic activity is induced, which is required for a nucleosome-specific histone H1-high-mobility group B exchange event and for local changes of chromatin architecture. Our data mechanistically link DNA topoisomerase IIbeta-dependent dsDNA breaks and the components of the DNA damage and repair machinery in regulated gene transcription.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Cell Line, Tumor
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Chromatin / metabolism
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Chromatin Immunoprecipitation
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DNA / metabolism*
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DNA Damage
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DNA Repair
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DNA Topoisomerases, Type II / metabolism*
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / metabolism*
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Enzyme Inhibitors / pharmacology
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Estradiol / pharmacology
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Estrogen Receptor alpha / metabolism
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Histones / metabolism
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Humans
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Membrane Proteins / genetics
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Nucleosomes / metabolism
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases / metabolism
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Presenilin-2
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Promoter Regions, Genetic
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Response Elements
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Thiobarbiturates / pharmacology
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Topoisomerase II Inhibitors
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Transcription Factors / metabolism
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Transcription, Genetic*
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Transcriptional Activation*
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Transfection
Substances
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Chromatin
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DNA-Binding Proteins
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Enzyme Inhibitors
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Estrogen Receptor alpha
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Histones
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Membrane Proteins
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Nucleosomes
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PSEN2 protein, human
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Presenilin-2
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Thiobarbiturates
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Topoisomerase II Inhibitors
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Transcription Factors
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Estradiol
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DNA
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PARP1 protein, human
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases
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DNA Topoisomerases, Type II
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merbarone