REKLES is an ARID3-restricted multifunctional domain

J Biol Chem. 2007 May 25;282(21):15768-77. doi: 10.1074/jbc.M700397200. Epub 2007 Mar 29.


Bright/Dril1/ARID3a is a B cell-specific, matrix association (or attachment) region-binding transcriptional regulator of immunoglobulin heavy chain genes and of E2F1-dependent cell cycle progression. Bright contains a central DNA binding domain termed ARID (AT-rich interacting domain) and a C-terminal region termed REKLES (for a conserved amino acid motif). The ARID domain has been identified in seven highly conserved families of metazoan proteins (ARID1-5 and JARID1-2), whereas REKLES is found only in the ARID3 subfamily (composed of Bright/ARID3a, Bdp/ARID3b, and Bright-like/ARID3c). REKLES consists of two subdomains: a modestly conserved N-terminal REKLESalpha and a highly conserved (among ARID3 orthologous proteins) C-terminal REKLESbeta. Previously we showed that Bright undergoes nucleocytoplasmic shuttling and that REKLESalpha and -beta were required, respectively, for nuclear import and Crm1-dependent nuclear export. Here we show that Bright further requires REKLESbeta for self-association or paralogue association and for nuclear matrix targeting. REK-LES promotes and regulates the extent of Bright multimerization, which occurs in the absence or presence of target DNA and is necessary for specific DNA binding. REKLESbeta-mediated interaction of Bright with Bdp, which localizes strictly to the nucleus, traps Bright within the nucleus via neutralization of its nuclear export activity. These results identify REKLES as a multifunctional domain that has co-evolved with and regulates functional properties of the ARID3 DNA binding domain.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Amino Acid Motifs / genetics
  • Animals
  • B-Lymphocytes / metabolism
  • COS Cells
  • Chlorocebus aethiops
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • E2F1 Transcription Factor / genetics
  • E2F1 Transcription Factor / metabolism
  • Eukaryota / genetics
  • Eukaryota / metabolism
  • Evolution, Molecular*
  • Humans
  • Immunoglobulin Heavy Chains / biosynthesis
  • Immunoglobulin Heavy Chains / genetics
  • Nuclear Matrix / genetics
  • Nuclear Matrix / metabolism
  • Oncogenes / genetics*
  • Organ Specificity / physiology
  • Protein Structure, Tertiary / genetics
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcription Factors


  • ARID3A protein, human
  • DNA-Binding Proteins
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Immunoglobulin Heavy Chains
  • Protozoan Proteins
  • Trans-Activators
  • Transcription Factors