Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition.
After fertilization, maternal factors direct development and trigger zygotic genome activation (ZGA) at the maternal-to-zygotic transition (MZT). In zebrafish, ZGA is required for gastrulation and clearance of maternal messenger RNAs, which is in part regulated by the conserved microRNA miR-430. However, the factors that activate the zygotic program in vertebrates are unknown. Here we show that Nanog, Pou5f1 (also called Oct4) and SoxB1 regulate zygotic gene activation in zebrafish. We identified several hundred genes directly activated by maternal factors, constituting the first wave of zygotic transcription. Ribosome profiling revealed that nanog, sox19b and pou5f1 are the most highly translated transcription factors pre-MZT. Combined loss of these factors resulted in developmental arrest before gastrulation and a failure to activate >75% of zygotic genes, including miR-430. Our results demonstrate that maternal Nanog, Pou5f1 and SoxB1 are required to initiate the zygotic developmental program and induce clearance of the maternal program by activating miR-430 expression.
1] Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA [2].
Miler T
MT
Lee
Ashley R
AR
Bonneau
Carter M
CM
Takacs
Ariel A
AA
Bazzini
Kate R
KR
DiVito
Elizabeth S
ES
Fleming
Antonio J
AJ
Giraldez
D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics; D009035:Mothers; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D059467:Transcriptome / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000378:metabolism*; D015053:Zygote / Q000378:metabolism*
D018398:Homeodomain Proteins; D035683:MicroRNAs; C557527:Mirn430 microRNA, zebrafish; D000071317:Nanog Homeobox Protein; C572119:Nanog protein, zebrafish; D050814:Octamer Transcription Factor-3; C085437:Pou5f3 protein, zebrafish; D055748:SOXB1 Transcription Factors; D029961:Zebrafish Proteins