Gene Expression Needs a Break to Unwind Before Carrying On

摘要

The lengthy genomic DNA of a eukaryotic cell manages to fit within the relatively small confines of its nucleus by spooling Twisting ribbons of DNA are tightly wrapped around core histone proteins, forming compact nucleosomes that constitute chromatin, the substance of chromosomes. Although this compacted structure is a means to handle space constraint, it presents a barrier to regulated genomic activity, including gene expression and maintenance of genomic integrity. However, cells are not adverselyaffected by such tight packaging because this highly structured assembly is compliant and dynamic, displaying varying degrees of compaction that allows regulated access to protein complexes in response to various stimuli. To operate within this overcrowded area, protein complexes locally remodel chromatin. But precisely how defined areas of chromatin adopt different conformations, allowing regulated access to specific DNA regions, is a captivating question. On page 1798 of this issue, Ju et al. (1) provide molecular evidence that the enzyme DNA topoisomerase IIbeta (TopoIIbeta) activates transcription by generating a break in double-stranded DNA within a nucleosome. This enzyme, which is associated with a DNA-repair machinery, allows chromatin to relax, which is needed to drive gene expression (see the figure).