Chromatin-bound Xenopus Dppa2 shapes the nucleus by locally inhibiting microtubule assembly.
Nuclear shape and size vary between species, during development, and in many tissue pathologies, but the causes and effects of these differences remain poorly understood. During fertilization, sperm nuclei undergo a dramatic conversion from a heavily compacted form into decondensed, spherical pronuclei, accompanied by rapid nucleation of microtubules from centrosomes. Here we report that the assembly of the spherical nucleus depends on a critical balance of microtubule dynamics, which is regulated by the chromatin-binding protein Developmental pluripotency-associated 2 (Dppa2). Whereas microtubules normally promote sperm pronuclear expansion, in Dppa2-depleted Xenopus egg extracts excess microtubules cause pronuclear assembly defects, leading to abnormal morphology and disorganized DNA replication. Dppa2 inhibits microtubule polymerization in vitro, and Dppa2 activity is needed at a precise time and location during nascent pronuclear formation. This demonstrates a strict spatiotemporal requirement for local suppression of microtubules during nuclear formation, fulfilled by chromatin-bound microtubule regulators.
Laboratory of Chromosome and Cell Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
John Z
JZ
Xue
Eileen M
EM
Woo
Lisa
L
Postow
Brian T
BT
Chait
Hironori
H
Funabiki
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002843:Chromatin / Q000378:metabolism*; D004261:DNA Replication; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D058105:Polymerization; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
D002843:Chromatin; C584866:Dppa2 protein, Xenopus; D009687:Nuclear Proteins; D029867:Xenopus Proteins