A pathway for mitotic chromosome formation

Mitotic chromosomes fold as compact arrays of chromatin loops.To identify the pathway of mitotic chromosome formation, we combined imaging and Hi-C analysis of synchronous DT40 cell cultures with polymer simulations. Here we show that in prophase, the interphase organization is rapidly lost in a condensin-dependent manner, and arrays of consecutive 60-kilobase (kb) loops are formed.During prometaphase, ~80-kb inner loops are nested within ~400-kb outer loops.The loop array acquires a helical arrangement with consecutive loops emanating from a central "spiral staircase" condensin scaffold.The size of helical turns progressively increases to ~12megabases during prometaphase. Acute depletion of condensin I or II shows that nested loops form by differential action of the two condensins, whereas condensin II is required for helical winding.National Human Genome Research Institute (Grant HG003143)National Institutes of Health Common Fund (Grant DK107980