A new long form of c-Maf cooperates with Sox9 to activate the type II collagen gene

J Biol Chem. 2002 Dec 27;277(52):50668-75. doi: 10.1074/jbc.M206544200. Epub 2002 Oct 14.

Abstract

A new long form of the c-Maf transcription factor (Lc-Maf) was identified and shown to interact specifically with SOX9 in a yeast two-hybrid cDNA library screening. Lc-Maf encodes an extra 10 amino acids at the carboxyl terminus of c-Maf and contains a different 3'-untranslated region compared with c-Maf. The interaction between SOX9 and Lc-Maf was further confirmed by co-immunoprecipitation and glutathione S-transferase pull-down assays, which mapped the interacting domain of SOX9 to the high mobility group box DNA binding domain and that of Lc-Maf to the basic leucine zipper motif. In situ hybridizations showed that Lc-Maf RNA was coexpressed with Sox9 and Col2a1 RNA in areas of precartilaginous mesenchymal condensations during mouse embryo development. A DNA binding site of Lc-Maf was identified at the 5'-end of a 48-bp Col2a1 enhancer element near the high mobility group binding site of SOX9. Lc-Maf and SOX9 synergistically activated a luciferase reporter plasmid containing a Col2a1 enhancer and increased the transcription of the endogenous Col2a1 gene. In summary, Lc-Maf is the first transcription factor shown to interact with Sox9, to be coexpressed with Sox9 during an early step of chondrogenesis and to cooperate with Sox9 in activating a downstream target gene of Sox9.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Chondrocytes / physiology
  • Collagen Type II / genetics*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Embryonic and Fetal Development
  • Gene Expression Regulation*
  • Gene Library
  • High Mobility Group Proteins / metabolism*
  • Humans
  • Lymphoma
  • Mice
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-maf
  • Recombinant Fusion Proteins / metabolism
  • SOX9 Transcription Factor
  • Sex Differentiation
  • Transcription Factors / metabolism*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Collagen Type II
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • MAF protein, human
  • Maf protein, mouse
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-maf
  • Recombinant Fusion Proteins
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Sox9 protein, mouse
  • Transcription Factors