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Mol Cell Biol, March 1998, p. 1322-1330, Vol. 18, No. 3
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

ETS-Core Binding Factor: a Common Composite Motif in Antigen Receptor Gene Enhancers

Batu Erman,1 Marta Cortes,1 Barbara S. Nikolajczyk,1 Nancy A. Speck,2 and Ranjan Sen1,*

Rosenstiel Research Center and Department of Biology, Brandeis University, Waltham, Massachusetts 02254,1 and Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 037552

Received 15 August 1997/Returned for modification 23 September 1997/Accepted 9 December 1997

A tripartite domain of the murine immunoglobulin µ heavy-chain enhancer contains the µA and µB elements that bind ETS proteins and the µE3 element that binds leucine zipper-containing basic helix-loop-helix (bHLH-zip) factors. Analysis of the corresponding region of the human µ enhancer revealed high conservation of the µA and µB motifs but a striking absence of the µE3 element. Instead of bHLH-zip proteins, we found that the human enhancer bound core binding factor (CBF) between the µA and µB elements; CBF binding was shown to be a common feature of both murine and human enhancers. Furthermore, mutant enhancers that bound prototypic bHLH-zip proteins but not CBF did not activate transcription in B cells, and conversely, CBF transactivated the murine enhancer in nonlymphoid cells. Taking these data together with the earlier analysis of T-cell-specific enhancers, we propose that ETS-CBF is a common composite element in the regulation of antigen receptor genes. In addition, these studies identify the first B-cell target of CBF, a protein that has been implicated in the development of childhood pre-B-cell leukemias.

* Corresponding author. Mailing address: Rosenstiel Research Center and Department of Biology, Brandeis University, Waltham, MA 02254. Phone: (781) 736-2455. Fax: (781) 736-2405. E-mail: sen{at}binah.cc.brandeis.edu.




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