CTCF is central to signaling pathways in immature B cells elicited by cross-linking the Ig BCR and stimulation with TGF? Both stimuli result in induction of cell cycle arrest and apoptosis. BCR ligation stimulates a transient induction of MYC that leads to high level CTCF expression and feedback suppression of MYC transcription. BCR ligation also activates PTEN opposing PI3K activation of MYC. Pharmacologic inactivation of PI3K or mTOR/FRAP results in suppression of S6K resulting in activation of CTCF and suppression of MYC. CTCF activation induces transcriptional activation of p19ARF, with its downstream consequences, and of p27. Growth arrest is occasioned by co-expression of p21 and p27 and inhibition of MYC. CTCF, is bona fide 憁ultivalent?DNA-sequence binder which specificity is mediated by different sets of zinc fingers (ZFs). For three different DNA target sites, particular groups of ZFs which cannot be deleted from the 11 ZF domain without loosing binding to a given site, are shown by a 憆ainbow?in the box on the left.
