Induction of immunoglobulin heavy-chain transcription through the transcription factor Bright requires TFII-I

Mol Cell Biol. 2006 Jun;26(12):4758-68. doi: 10.1128/MCB.02009-05.

Abstract

Bright/ARID3a/Dril1, a member of the ARID family of transcription factors, is expressed in a highly regulated fashion in B lymphocytes, where it enhances immunoglobulin transcription three- to sixfold. Recent publications from our lab indicated that functional, but not kinase-inactive, Bruton's tyrosine kinase (Btk) is critical for Bright activity in an in vitro model system, yet Bright itself is not appreciably tyrosine phosphorylated. These data suggested that a third protein, and Btk substrate, must contribute to Bright-enhanced immunoglobulin transcription. The ubiquitously expressed transcription factor TFII-I was identified as a substrate for Btk several years ago. In this work, we show that TFII-I directly interacts with human Bright through amino acids in Bright's protein interaction domain and that specific tyrosine residues of TFII-I are essential for Bright-induced activity of an immunoglobulin reporter gene. Moreover, inhibition of TFII-I function in a B-cell line resulted in decreased heavy-chain transcript levels. These data suggest that Bright functions as a three-component protein complex in the immunoglobulin locus and tie together previous data indicating important roles for Btk and TFII-I in B lymphocytes.

Publication types

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

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Base Sequence
  • Binding Sites
  • Cell Line
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Genes, Immunoglobulin*
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Mice
  • Mutation
  • Oncogenes / genetics
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Trans-Activators / chemistry
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors
  • Transcription Factors, TFII / genetics
  • Transcription Factors, TFII / metabolism*
  • Transcription, Genetic

Substances

  • ARID3A protein, human
  • DNA-Binding Proteins
  • GTF2I protein, human
  • Immunoglobulin Heavy Chains
  • RNA, Messenger
  • Trans-Activators
  • Transcription Factors
  • Transcription Factors, TFII
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Btk protein, mouse