Corl1, a novel neuronal lineage-specific transcriptional corepressor for the homeodomain transcription factor Lbx1.
During development, neuronal identity is determined by a combination of numerous transcription factors. However, the mechanisms of synergistic action of these factors in transcriptional regulation and subsequent cell fate specification are largely unknown. In this study, we identified a novel gene, Corl1, encoding a nuclear protein with homology to the Ski oncoprotein. Corl1 was highly selectively expressed in the central nervous system (CNS). In the embryonic CNS, Corl1 was expressed in a certain subset of postmitotic neurons generated posterior to the midbrain-hindbrain border. In the developing spinal cord, Corl1 was selectively expressed in the dorsal horn interneurons where a homeodomain transcription factor, Lbx1, is required for proper specification. Corl1 was localized in a nuclear dot-like structure and interacted with general transcriptional corepressors. In addition, Corl1 showed transcriptional repression activity in the GAL4-fusion system, indicating its involvement in the regulation of transcriptional repression. Furthermore, Corl1 interacted with Lbx1 and cooperatively repressed transcription, suggesting that it acts as a transcriptional corepressor for Lbx1 in regulating cell fate determination in the dorsal spinal cord. Corl1 corepressor activity did not depend on Gro/TLE activity, and Gro/TLE also functioned as a corepressor for Lbx1. Thus, Lbx1 can select two independent partners, Corl1 and Gro/TLE, as corepressors. Identification of a novel transcriptional corepressor with neuronal subtype-restricted expression might provide insights into the mechanisms of cell fate determination in neurons.
Mizuhara
Eri
E
KAN Research Institute Inc., 93 Chudoji-Awata-cho, Shimogyo-ku, Kyoto 600-8815, Japan.
Nakatani
Tomoya
T
Minaki
Yasuko
Y
Sakamoto
Yoshimasa
Y
Ono
Yuichi
Y
D000595:Amino Acid Sequence; D000818:Animals; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D007395:Interneurons / Q000502:physiology*; D008636:Mesencephalon / Q000166:cytology / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*
C497819:Corl1 protein, mouse; D004268:DNA-Binding Proteins; C491868:Lbx1h protein, mouse; D009124:Muscle Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C512653:Ski protein, mouse