A pathway for mitotic chromosome formation
Johan H. Gibcus1,*, Kumiko Samejima2,*, Anton
Goloborodko3,*, Itaru Samejima2, Natalia Naumova1, Johannes Nuebler3, Masato T.
Kanemaki4, Linfeng Xie5, James R. Paulson5, William C. Earnshaw2,†, Leonid A.
Mirny3,†, Job Dekker1,6,†
1Program in Systems Biology, Department of
Biochemistry and Molecular Pharmacology, University of Massachusetts Medical
School, 368 Plantation Street, Worcester, MA 01605, USA.
2Wellcome Centre for Cell Biology University of
Edinburgh, King’s Buildings, Max Born Crescent Edinburgh EH9 3BF, Scotland, UK.
3Institute for Medical Engineering and Science,
and Department of Physics, Massachusetts Institute of Technology, Cambridge, MA
02139, USA.
4Division of Molecular Cell Engineering,
National Institute of Genetics, Research Organization of Information and
Systems (ROIS), and Department of Genetics, SOKENDAI, Yata 1111, Mishima,
Shizuoka 411-8540, Japan.
5Department of Chemistry, University of
Wisconsin-Oshkosh, 800 Algoma Blvd, Oshkosh, WI 54901, USA.
6Howard Hughes Medical Institute, 4000 Jones
Bridge Road, Chevy Chase, MD 20815-6789, USA.
↵†Corresponding
author. Email: bill.earnshaw@ed.ac.uk (W.C.E.); leonid@MIT.edu (L.A.M.);
job.dekker@umassmed.edu (J.D.)
↵* These authors contributed equally to this work.
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Science
18 Jan 2018:
eaao6135
Source/Fonte: Anton Goloborodko
Abstract
Mitotic chromosomes fold as compact arrays of
chromatin loops. To identify the pathway of mitotic chromosome formation, we
combined imaging and Hi-C of synchronous DT40 cell cultures with polymer
simulations. We show that in prophase, the interphase organization is rapidly
lost in a condensin-dependent manner and arrays of consecutive 60 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 during prometaphase to ~12 Mb. Acute
depletion of condensin I or II shows that nested loops form by differential
action of the two condensins while condensin II is required for helical
winding.
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