Characterization of ABF-1, a Novel Basic Helix-Loop-Helix Transcription Factor Expressed in Activated B Lymphocytes

ABSTRACT

Proteins of the basic helix-loop-helix (bHLH) family are required for a number of different developmental pathways, including neurogenesis, lymphopoiesis, myogenesis, and sex determination. Using a yeast two-hybrid screen, we have identified a new bHLH transcription factor, ABF-1, from a human B-cell cDNA library. Within the bHLH region, ABF-1 shows a remarkable conservation with other HLH proteins, including tal-1, NeuroD, and paraxis. Its expression pattern is restricted to a subset of lymphoid tissues, Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines, and activated human B cells. ABF-1 is capable of binding an E-box element either as a homodimer or as a heterodimer with E2A. Furthermore, a heterodimeric complex containing ABF-1 and E2A can be detected in EBV-immortalized lymphoblastoid cell lines. ABF-1 contains a transcriptional repression domain and is capable of inhibiting the transactivation capability of E47 in mammalian cells. ABF-1 represents the first example of a B-cell-restricted bHLH protein, and its expression pattern suggests that ABF-1 may play a role in regulating antigen-dependent B-cell differentiation.

ACKNOWLEDGMENTS

We thank the following individuals for their contributions to this work: Ingrid Wolvers-Tettero for assistance with Northern blots; Maarten Stuiver and Gretchen Bain for valuable discussions; Barbara Kee for critical reading of the manuscript; Johan van Es for LCLs and advice; Bettina Kempkes for the conditional ER/EB2-5 cell line; Marieke Griffioen for the hEF-1α cDNA; Steve Elledge for two-hybrid reagents; and Michael G. Rosenfeld for the 3xUAS-TK LUC reporter plasmid.

This work was supported by the National Institutes of Health, the Council for Tobacco Research, and the Edward Mallinckrodt Jr. Foundation.