GPS para cromossomos - Reorganização do genoma durante o desenvolvimento: mero acaso, fortuita necessidade ou design inteligente?

segunda-feira, março 02, 2020

Molecular Cell

Available Online 26 February 2020

Lamina-Dependent Stretching and Unconventional Chromosome Compartments in Early C. elegans Embryos

Ahilya N.Sawh 1, 2 Maxwell E.R.Shafer 1, 2 Jun-HanSu 3 Xiaowei Zhuang 3 Siyuan Wang 3, 4 Susan E.Mango 1, 2, 5

Biozentrum, University of Basel, 4056 Basel, Switzerland

Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA

Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Department of Physics, Harvard University, Cambridge, MA 02138, USA

Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA

Received 19 May 2019, Revised 20 November 2019, Accepted 4 February 2020, Available online 26 February 2020.

Published: February 26, 2020


• Chromosomes from early embryos resemble a barbell

• Lamina interactions stretch chromosomes and separate compartments

• Conventional compartments arise during gastrulation via long-distance associations

• Single-chromosome clustering uncovers prevalent conformations


Current models suggest that chromosome domains segregate into either an active (A) or inactive (B) compartment. B-compartment chromatin is physically separated from the A compartment and compacted by the nuclear lamina. To examine these models in the developmental context of C. elegans embryogenesis, we undertook chromosome tracing to map the trajectories of entire autosomes. Early embryonic chromosomes organized into an unconventional barbell-like configuration, with two densely folded B compartments separated by a central A compartment. Upon gastrulation, this conformation matured into conventional A/B compartments. We used unsupervised clustering to uncover subpopulations with differing folding properties and variable positioning of compartment boundaries. These conformations relied on tethering to the lamina to stretch the chromosome; detachment from the lamina compacted, and allowed intermingling between, A/B compartments. These findings reveal the diverse conformations of early embryonic chromosomes and uncover a previously unappreciated role for the lamina in systemic chromosome stretching.

Keywords 3D genome chromosome conformation multiplexed DNA FISH unsupervised clustering early embryogenesis nuclear lamina development


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