Gtx, an oligondendrocyte-specific homeodomain protein, has repressor activity

Raj Awatramani, Jacqueline Beesley, Huibin Yang, Huiyuan Jiang, Franca Cambi, Judith Grinspan, James Garbern, John Kamholz*

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Myelin, a multilamellar membrane structure that facilitates nerve conduction, is synthesized in the central nervous system (CNS) by oligodendrocytes. Gtx, a member of the homeodomain family of transcriptional factors, is a candidate regulator of myelin gene expression, because it is uniquely expressed in myelinating oligodendrocytes in postnatal rodent brain. To analyze the regulatory activity of Gtx, we first identified the optimal Gtx-binding sequence using an in vitro DNA-binding assay. This sequence, (A/T)TTAATGA, contains a TAAT core and is similar, but not identical, to that of other homeodomain protein binding sites. When coexpressed in cultured cells along with a minimal promoter containing five tandem repeats of this optimal Gtx-binding sequence, Gtx demonstrated repressor activity, which was also present when Gtx was tethered to DNA by way of the strong GAL4 DNA-binding domain. Truncations of the GAL4-Gtx fusion identified a portable repressor domain within a relatively proline/alanine-rich region N-terminal to the Gtx homeodomain. Cotransfection of a Gtx expression vector into a variety of cell lines, including oligodendrocytes, along with constructs containing portions of the PLP, MBP, or Gtx promoters fused to a reporter gene, however, did not modulate transcription from any of these promoter constructs. These data support the notion that the oligodendrocyte-specific homeodomain protein Gtx can act as a transcriptional repressor. In addition, they suggest that interaction of Gtx with other, as yet undefined, transcriptional regulators modifies Gtx activity in oligodendrocytes. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)376-387
Number of pages12
JournalJournal of Neuroscience Research
Volume61
Issue number4
DOIs
StatePublished - Aug 15 2000

Keywords

  • Gene regulation
  • Gtx
  • Homeodomain
  • Myelin
  • Oligodendrocyte
  • Repressor

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Gtx, an oligondendrocyte-specific homeodomain protein, has repressor activity'. Together they form a unique fingerprint.

  • Cite this