focus on a single target is also seen for polycomb group (PcG) proteins. These proteins mediate transcriptional repression and often oppose the function of trithorax group (TrxG) genes such as those encoding BRG1 and MLL (discussed in the next section), by regulating chromatin structure. Early developmental effects of mutations in the mouse PcG gene Ring1b (also known as Rnf2) can be partly repressed by a mutation in Ink4a (also known as Cdkn2a or Arf), which is a BMI1-target gene and cell-cycle inhibitor14. In addition, late developmental effects of Bmi1 mutation can be partly repressed by null mutations of Chk2 (also known as Chek2), which normally induces a checkpoint evoked by the mitochondrial dysfunction in Bmi1-mutant mice15. Furthermore, the neural developmental phenotypes of mice lacking the TrxG protein MLL, can be reversed by rescuing expression of just one of its targets, Dlx2 (ref. 16). The surprising dedication of chromatin regulators to a single gene suggests that in vitro studies of mechanism will need to focus on appropriate biological targets in the correct cell type.
