A strand-specific burst in transcription of pericentric satellites is required for chromocenter formation and early mouse development.
At the time of fertilization, the paternal genome lacks the typical configuration and marks characteristic of pericentric heterochromatin. It is thus essential to understand the dynamics of this region during early development, its importance during that time period and how a somatic configuration is attained. Here, we show that pericentric satellites undergo a transient peak in expression precisely at the time of chromocenter formation. This transcription is regulated in a strand-specific manner in time and space and is strongly biased by the parental asymmetry. The transcriptional upregulation follows a developmental clock, yet when replication is blocked chromocenter formation is impeded. Furthermore, interference with major satellite transcripts using locked nucleic acid (LNA)-DNA gapmers results in developmental arrest before completion of chromocenter formation. We conclude that the exquisite strand-specific expression dynamics at major satellites during the 2-cell stage, with both up and downregulation, are necessary events for proper chromocenter organization and developmental progression.
Laboratory of Nuclear Dynamics and Genome Plasticity, Unité Mixte de Recherche, 218 Centre National de la Recherche Scientifique/Institut Curie, 26, rue d'Ulm, 75248 Paris Cedex 05, France.
Aline V
AV
Probst
Ikuhiro
I
Okamoto
Miguel
M
Casanova
Fatima
F
El Marjou
Patricia
P
Le Baccon
Geneviève
G
Almouzni
D000818:Animals; D002970:Cleavage Stage, Ovum / Q000166:cytology / Q000378:metabolism; D004276:DNA, Satellite / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006570:Heterochromatin / Q000235:genetics*; D008297:Male; D051379:Mice; D010312:Parthenogenesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D016196:S Phase / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics
D004276:DNA, Satellite; D006570:Heterochromatin; D012333:RNA, Messenger