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

Full 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.

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Author information

Author/s: Rajaiya, Jaya (J); Nixon, Jamee C (JC); Ayers, Neil (N); Desgranges, Zana P (ZP); Roy, Ananda L (AL); Webb, Carol F (CF);

Affiliation: Oklahoma Medical Research Foundation, Immunobiology and Cancer Research Program, 825 N. E. 13th Street, Oklahoma City, OK 73104, USA.

Grants: AI044215 (Agency:NIAID NIH HHS) ; AI45150 (Agency:NIAID NIH HHS) ; C06 RR14570-01 (Agency:NCRR NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Molecular and cellular biology (Mol Cell Biol), published in United States. (Language: eng)

Reference: 2006-Jun; vol 26 (issue 12) : pp 4758-68

Dates: Created 2006/06/01; Completed 2006/07/17; Revised 2008/11/20;

PMID: 16738337, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
B-Lymphocytes - immunology; metabolism
Base Sequence
Binding Sites
Cell Line
DNA-Binding Proteins - chemistry; genetics; metabolism
Genes, Immunoglobulin
Humans
Immunoglobulin Heavy Chains - genetics

Mice
Mutation
Oncogenes - genetics
Protein Structure, Tertiary
Protein-Tyrosine Kinases - metabolism
RNA, Messenger - genetics; metabolism
Trans-Activators - chemistry; genetics; metabolism
Transcription Factors, TFII - genetics; metabolism
Transcription, Genetic

Associated Chemicals: ARID3A protein, human (0) ; DNA-Binding Proteins (0) ; GTF2I protein, human (0) ; Immunoglobulin Heavy Chains (0) ; RNA, Messenger (0) ; Trans-Activators (0) ; Transcription Factors, TFII (0) ; Agammaglobulinaemia tyrosine kinase (EC 2.7.1.112) ; Protein-Tyrosine Kinases (EC 2.7.1.112)

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