Empacotando um genoma passo a passo: mero acaso, fortuita necessidade ou design inteligente?

domingo, janeiro 21, 2018

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:
Source/Fonte: Anton Goloborodko

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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