Acetylated YY1 regulates Otx2 expression in anterior neuroectoderm at two cis-sites 90 kb apart.
The mouse homeobox gene Otx2 plays essential roles at each step and in every tissue during head development. We have previously identified a series of enhancers that are responsible for driving the Otx2 expression in these contexts. Among them the AN enhancer, existing 92 kb 5' upstream, directs Otx2 expression in anterior neuroectoderm (AN) at the headfold stage. Analysis of the enhancer mutant Otx2(DeltaAN/-) indicated that Otx2 expression under the control of this enhancer is essential to the development of AN. This study demonstrates that the AN enhancer is promoter-dependent and regulated by acetylated YY1. YY1 binds to both the AN enhancer and promoter region. YY1 is acetylated in the anterior head, and only acetylated YY1 can bind to the sequence in the enhancer. Moreover, YY1 binding to both of these two sites is essential to Otx2 expression in AN. These YY1 binding sites are highly conserved in AN enhancers in tetrapods, coelacanth and skate, suggesting that establishment of the YY1 regulation coincides with that of OTX2 function in AN development in an ancestral gnathostome.
Takasaki
Nobuyoshi
N
Laboratory for Vertebrate Body Plan, Center for Developmental Biology (CDB), RIKEN Kobe, Chuo-ku, Kobe, Japan.
Kurokawa
Daisuke
D
Nakayama
Rika
R
Nakayama
Jun-Ichi
J
Aizawa
Shinichi
S
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004475:Ectoderm / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D008156:Luciferases; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D051857:Otx Transcription Factors / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017385:Sequence Homology; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse; D008156:Luciferases