Higher chromatin mobility supports totipotency and precedes pluripotency in vivo.
The fusion of the gametes upon fertilization results in the formation of a totipotent cell. Embryonic chromatin is expected to be able to support a large degree of plasticity. However, whether this plasticity relies on a particular conformation of the embryonic chromatin is unknown. Moreover, whether chromatin plasticity is functionally linked to cellular potency has not been addressed. Here, we adapted fluorescence recovery after photobleaching (FRAP) in the developing mouse embryo and show that mobility of the core histones H2A, H3.1, and H3.2 is unusually high in two-cell stage embryos and decreases as development proceeds. The transition toward pluripotency is accompanied by a decrease in histone mobility, and, upon lineage allocation, pluripotent cells retain higher mobility than the differentiated trophectoderm. Importantly, totipotent two-cell-like embryonic stem cells also display high core histone mobility, implying that reprogramming toward totipotency entails changes in chromatin mobility. Our data suggest that changes in chromatin dynamics underlie the transitions in cellular plasticity and that higher chromatin mobility is at the nuclear foundations of totipotency.
CNRS/INSERM U964, Université de Strasbourg, Institut de Génétique et de Biologie Moléculaire et Cellulaire, F-67404 Illkirch, France;
Ana
A
Bošković
CNRS/INSERM U964, Université de Strasbourg, Institut de Génétique et de Biologie Moléculaire et Cellulaire, F-67404 Illkirch, France;
André
A
Eid
CNRS/INSERM U964, Université de Strasbourg, Institut de Génétique et de Biologie Moléculaire et Cellulaire, F-67404 Illkirch, France;
Julien
J
Pontabry
CNRS/INSERM U964, Université de Strasbourg, Institut de Génétique et de Biologie Moléculaire et Cellulaire, F-67404 Illkirch, France;
Takashi
T
Ishiuchi
CNRS/INSERM U964, Université de Strasbourg, Institut de Génétique et de Biologie Moléculaire et Cellulaire, F-67404 Illkirch, France;
Coralie
C
Spiegelhalter
Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Edupuganti V S
EV
Raghu Ram
Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Eran
E
Meshorer
CNRS/INSERM U964, Université de Strasbourg, Institut de Génétique et de Biologie Moléculaire et Cellulaire, F-67404 Illkirch, France;
Maria-Elena
ME
Torres-Padilla
D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism / Q000648:ultrastructure; D053595:Embryonic Stem Cells / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D046529:Microscopy, Electron, Transmission; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D039901:Totipotent Stem Cells / Q000378:metabolism*
D002843:Chromatin; D006657:Histones
cell fate; chromatin dynamics; pluripotency; reprogramming; totipotent cells