CBP and p300 coactivators contribute to the maintenance of Isl1 expression by the Onecut transcription factors in embryonic spinal motor neurons.

Onecut transcription factors are required to maintain Islet1 (Isl1) expression in developing spinal motor neurons (MNs), and this process is critical for proper MN differentiation. However, the mechanisms whereby OC stimulate Isl1 expression remain unknown. CREB-binding protein (CBP) and p300 paralogs are transcriptional coactivators that interact with OC proteins in hepatic cells. In the embryonic spinal cord, CBP and p300 play key roles in neurogenesis and MN differentiation. Here, using chromatin immunoprecipitation and in ovo electroporation in chicken spinal cord, we provide evidence that CBP and p300 contribute to the regulation of Isl1 expression by the OC factors in embryonic spinal MNs. CBP and p300 are detected on the CREST2 enhancer of Isl1 where OC factors are also bound. Inhibition of CBP and p300 activity inhibits activation of the CREST2 enhancer and prevents the stimulation of Isl1 expression by the OC factors. These observations suggest that CBP and p300 coactivators cooperate with OC factors to maintain Isl1 expression in postmitotic MNs.