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 ~12 megabases 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.
Gibcus JH • Samejima K • Goloborodko A • Samejima I • Naumova N • Nuebler J • Kanemaki MT • Xie L • Paulson JR • Earnshaw WC • Mirny LA • Dekker J
Science (New York, N.Y.)
February 9th, 2018
About this Study
This study takes advantage of the chicken cell line DT40 with a Cdk1as (analog-sensitive) mutant, in which Cdk1 can be inactivated with 1NM-PP1 in order to synchronize the cells. This allows the authors to perform Hi-C on cells at different stages of mitosis, and they compare control cells to cells with condensin I or II depleted to look at chromosome condensation and the relative contribution of the condensins.