Regulation of the mitotic chromosome folding machines

Over the last several years enormous progress has been made in identifying the molecu-lar machines, including condensins and topoisomerases that fold mitotic chromosomes. The discovery that condensins generate chromatin loops through loop extrusion has revolutionized, and energized, the field of chromosome folding. To understand how these machines fold chromosomes with the appropriate dimensions, while disentangling sister chromatids, it needs to be determined how they are regulated and deployed. Here, we outline the current understanding of how these machines and factors are regulated through cell cycle dependent expression, chromatin localization, activation and inactiva-tion through post-translational modifications, and through associations with each other, with other factors and with the chromatin template itself. There are still many open ques-tions about how condensins and topoisomerases are regulated but given the pace of pro-gress in the chromosome folding field, it seems likely that many of these will be answered in the years ahead.

Automated summary

Significant progress has been made in identifying the molecular machines involved in chromosome folding, such as condensins and topoisomerases, in recent years. The discovery of condensins generating chromatin loops through loop extrusion has greatly impacted and energized the field. Current understanding suggests that these machines and factors are regulated through cell cycle dependent expression, chromatin localization, post-translational modifications, and associations with other factors and the chromatin template. Although there are still unanswered questions about the regulation of condensins and topoisomerases, it is likely that many of these will be addressed in the future, given the pace of progress in the field of chromosome folding.