First Author | Lee S | Year | 2013 |
Journal | Proc Natl Acad Sci U S A | Volume | 110 |
Issue | 28 | Pages | 11445-50 |
PubMed ID | 23798382 | Mgi Jnum | J:198703 |
Mgi Id | MGI:5499026 | Doi | 10.1073/pnas.1302676110 |
Citation | Lee S, et al. (2013) STAT3 promotes motor neuron differentiation by collaborating with motor neuron-specific LIM complex. Proc Natl Acad Sci U S A 110(28):11445-50 |
abstractText | The motor neuron (MN)-hexamer complex consisting of LIM homeobox 3, Islet-1, and nuclear LIM interactor is a key determinant of motor neuron specification and differentiation. To gain insights into the transcriptional network in motor neuron development, we performed a genome-wide ChIP-sequencing analysis and found that the MN-hexamer directly regulates a wide array of motor neuron genes by binding to the HxRE (hexamer response element) shared among the target genes. Interestingly, STAT3-binding motif is highly enriched in the MN-hexamer-bound peaks in addition to the HxRE. We also found that a transcriptionally active form of STAT3 is expressed in embryonic motor neurons and that STAT3 associates with the MN-hexamer, enhancing the transcriptional activity of the MN-hexamer in an upstream signal-dependent manner. Correspondingly, STAT3 was needed for motor neuron differentiation in the developing spinal cord. Together, our studies uncover crucial gene regulatory mechanisms that couple MN-hexamer and STAT-activating extracellular signals to promote motor neuron differentiation in vertebrate spinal cord. |