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Publication : Variant PRC1 competes with retinoic acid-related signals to repress <i>Meis2</i> in the mouse distal forelimb bud.

First Author  Yakushiji-Kaminatsui N Year  2018
Journal  Development Volume  145
Issue  19 PubMed ID  30190278
Mgi Jnum  J:293527 Mgi Id  MGI:6452911
Doi  10.1242/dev.166348 Citation  Yakushiji-Kaminatsui N, et al. (2018) Variant PRC1 competes with retinoic acid-related signals to repress Meis2 in the mouse distal forelimb bud. Development 145(19):dev166348
abstractText  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.
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