10 p.-3 fig.-1 tab.Suppression of Meis genes in the distal limb bud is required for proximal-distal (PD) specification of the forelimb. Polycomb group (PcG) factors play a role in downregulation of retinoic acid (RA)-related signals in the distal forelimb bud, causing Meis repression. It is, however, not known whether downregulation of RA-related signals and PcG-mediated proximal gene repression are functionally linked. Here, we reveal that PcG factors and RA-related signals antagonize each other to polarize Meis2 expression along the PD axis in mouse. Supported by mathematical modeling and simulation, we propose that PcG factors are required to adjust the threshold for RA-related signaling to regulate Meis2 expression. Finally, we show that a variant Polycomb repressive complex 1 (PRC1), incorporating PCGF3 and PCGF5, represses Meis2 expression in the distal limb bud. Taken together, we reveal a previously unknown link between PcG proteins and downregulation of RA-related signals to mediate the phase transition of Meis2 transcriptional status during forelimb patterning.This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) (23249015 to H.K.), the Japan Agency for Medical Research and Development (AMED) (JP18gm0510016 to H.K. and T.K.), the Special Postdoctoral Researcher Program of RIKEN (to N.Y.-K.), the Regional Innovation Program from MEXT (to T.K.) and the Cross-ministerial Strategic Innovation Promotion Program (SIP) from Cabinet Office, Government of Japan (to T.K. and H.K.).Peer reviewe
