Induction of immunoglobulin heavy-chain transcription through the transcription factor Bright requires TFII-I.
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.
Rajaiya
Jaya
J
Oklahoma Medical Research Foundation, Immunobiology and Cancer Research Program, 825 N. E. 13th Street, Oklahoma City, OK 73104, USA.
Nixon
Jamee C
JC
Ayers
Neil
N
Desgranges
Zana P
ZP
Roy
Ananda L
AL
Webb
Carol F
CF
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D051379:Mice; D009154:Mutation; D009857:Oncogenes / Q000235:genetics; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D019473:Transcription Factors, TFII / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
C490798:ARID3A protein, human; D004268:DNA-Binding Proteins; C104259:GTF2I protein, human; D007143:Immunoglobulin Heavy Chains; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse