Topoisomerase IIbeta activates a subset of neuronal genes that are repressed in AT-rich genomic environment.

PloS One
Kuniaki SanoKen Tsutsui

Abstract

DNA topoisomerase II (topo II) catalyzes a strand passage reaction in that one duplex is passed through a transient brake or gate in another. Completion of late stages of neuronal development depends on the presence of active beta isoform (topo IIbeta). The enzyme appears to aid the transcriptional induction of a limited number of genes essential for neuronal maturation. However, this selectivity and underlying molecular mechanism remains unknown. Here we show a strong correlation between the genomic location of topo IIbeta action sites and the genes it regulates. These genes, termed group A1, are functionally biased towards membrane proteins with ion channel, transporter, or receptor activities. Significant proportions of them encode long transcripts and are juxtaposed to a long AT-rich intergenic region (termed LAIR). We mapped genomic sites directly targeted by topo IIbeta using a functional immunoprecipitation strategy. These sites can be classified into two distinct classes with discrete local GC contents. One of the classes, termed c2, appears to involve a strand passage event between distant segments of genomic DNA. The c2 sites are concentrated both in A1 gene boundaries and the adjacent LAIR, suggesting a direct link b...Continue Reading

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Datasets Mentioned

BETA
AB262979

Methods Mentioned

BETA
immunoprecipitation
PCR
electrophoresis
RNA Assay
transfection
Profiler
Human Genome Sequencing
ChIP-chip

Software Mentioned

13
Profiler
GOstat2
GENios
MySQL
BLAT
Excel
Orth Profiler
GeneChip Operating Software ( GCOS
: Convert

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