Corl1, a novel neuronal lineage-specific transcriptional corepressor for the homeodomain transcription factor Lbx1

J Biol Chem. 2005 Feb 4;280(5):3645-55. doi: 10.1074/jbc.M411652200. Epub 2004 Nov 4.

Abstract

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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Lineage
  • DNA-Binding Proteins / genetics
  • Gene Expression / physiology
  • Interneurons / physiology*
  • Mesencephalon / cytology
  • Mesencephalon / physiology
  • Mice
  • Molecular Sequence Data
  • Muscle Proteins / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Spinal Cord / cytology
  • Spinal Cord / physiology
  • Transcription, Genetic / physiology*

Substances

  • Corl1 protein, mouse
  • DNA-Binding Proteins
  • Lbx1h protein, mouse
  • Muscle Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Ski protein, mouse

Associated data

  • GENBANK/AB185113