Polycomb repressive complex 2 (PRC2) directs methylation of histone H3 K27 (H3K27me), a repressive histone mark. Mutations in PRC2 complex components cause a spectrum of developmental defects, including posterior transformation of the skeleton due to misexpression of Hox cluster genes. In addition to the core complex components, a number of substoichiometric accessory proteins have been identified, but the functions of these remain incompletely understood. One of these factors is AEBP2, a zinc-finger domain-containing protein that has been proposed to play a role in PRC2 recruitment. On p. , Sarah Cooper, Neil Brockdorff and colleagues evaluate the role of AEBP2, generating a knockout mouse and mutant embryonic stem cells (ESCs). Surprisingly, the phenotype observed upon Aebp2 depletion is not loss of PRC2 function, but rather a Trithorax phenotype (anteriorisation of the skeleton) associated with increased Polycomb activity. In the absence of Aebp2, an atypical PRC2 complex appears to form, which may be responsible for the mild enhancement in H3K27me levels. The authors therefore propose that AEBP2 functions primarily to define the composition of PRC2 complexes, and hence modulate their activity.
