Polycomb group (PcG) proteins play important roles in regulating gene expression during development but how they contribute to patterning and morphogenetic processes, particularly during mammalian development, is unclear. Here, Haruhiko Koseki and colleagues show that RING1 proteins, which are essential components of Polycomb repressive complex-1 (PRC1), control proximal-distal patterning of the mouse forelimb (p. ). They demonstrate that Ring1A/B knockout embryos display severe defects in forelimb formation. By analysing gene expression in the distal and proximal regions of the forelimbs in control and mutant animals, they researchers report that RING1 proteins repress the proximal limb regulatory programme in the distal limb bud. Chromatin immunoprecipitation assays reveal that the gene encoding the transcription factor Meis – a known proximal limb bud marker – is bound by RING1 proteins, suggesting that Ring1A/B restrict Meis expression to the proximal limb bud; in line with this, the depletion of Meis2 partially restores distal gene expression and limb formation in Ring1-deficient mice. These and other findings lead the authors to propose that PcG factors integrate developmental signals at genes encoding critical transcription factors to regulate patterning during development.
