Activation of Xenopus genes required for lateral inhibition and neuronal differentiation during primary neurogenesis

XNGN-1, a member of the neurogenin family of basic helix-loop-helix protein s, plays a critical role in promoting neuronal differentiation in Xenopus e mbryos. When ectopically expressed, XNGN-1 induces the expression of a set of genes required for neuronal differentiation such as XMyT1 and NeuroD. At the same time, however, XNGN-1 induces the expression of genes that antago nize neuronal differentiation by a process called lateral inhibition. Here, we present evidence that XNGN-1 activates the expression of genes required for differentiation and lateral inhibition by recruiting transcriptional c oactivators p300/CBP (CREB-binding protein) or PCAF (p300/CBP-associated pr otein), both of which contain histone acetyltransferase (HAT) activity. Sig nificantly, transcriptional activation of the genes in the lateral inhibito ry pathway is less dependent an the HAT activity than is the activation of the genes that mediate differentiation. We propose that this difference ena bles the genes in the lateral inhibition pathway to be induced prior to the genes that promote differentiation, thus enabling lateral inhibition to es tablish a negative feedback loop and restrict the number of cells undergoin g neuronal differentiation.