The miR-302 cluster transcriptionally regulated by POUV, SOX and STAT5B controls the undifferentiated state through the post-transcriptional repression of PBX3 and E2F7 in early chick development.
Early chick development is a systematic process governed by the concerted action of multiple mechanisms that regulate transcription and post-transcriptional processes. Post-transcriptional microRNA-mediated regulation, with regard to lineage specification and differentiation in early chick development, requires further investigation. Here, we characterize the transcriptional and post-transcriptional regulation mechanisms in undifferentiated chick blastodermal cells. Expression of the miR-302 cluster, POUV, SOX2, and STAT5B decreased in a time-dependent manner in early chick development. We found that POUV, SOX2, and STAT5B regulate the transcription of the miR-302 cluster, as its 5'-flanking region contains binding elements for each transcription factor. Additionally, POUV, SOX2, and STAT5B maintain pluripotency by regulating genes containing the miR-302 cluster target sequence. For example, microRNAs from the miR-302 cluster can bind to PBX3 and E2F7 transcripts, thus acting as a post-transcriptional regulator that maintains the undifferentiated state of blastodermal cells by balancing the expression of genes related to pluripotency and differentiation. Based on these results, we suggest that both transcriptional and post-transcriptional regulation of the miR302 cluster is critical for intrinsically controlling the undifferentiated state of chick embryonic blastodermal cells. These findings may help our understanding of the cellular and molecular mechanisms that underlie developmental decisions during early chick development.
Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Suwon, 441-706, Republic of Korea.
Sang In
SI
Lee
Mi-Hyang
MH
Jeon
Jeom Sun
JS
Kim
Jin-Ki
JK
Park
Eung-Woo
EW
Park
Ik-Soo
IS
Jeon
Sung June
SJ
Byun
D000818:Animals; D002642:Chick Embryo / Q000196:embryology* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D008156:Luciferases; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D034622:RNA Interference / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055747:SOX Transcription Factors / Q000502:physiology; D050799:STAT5 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D017931:DNA Primers; D035683:MicroRNAs; D055747:SOX Transcription Factors; D050799:STAT5 Transcription Factor; D014157:Transcription Factors; D008156:Luciferases