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Molecular and Cellular Biology, January 2003, p. 259-271, Vol. 23, No. 1
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.1.259-271.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Novel Transcriptional Potentiation of BETA2/NeuroD on the Secretin Gene Promoter by the DNA-Binding Protein Finb/RREB-1

Subir K. Ray, Junko Nishitani,{dagger} Mary W. Petry, Michael Y. Fessing, and Andrew B. Leiter*

Division of Gastroenterology, GRASP Digestive Disease Center, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts

Received 9 August 2002/ Returned for modification 17 September 2002/ Accepted 18 October 2002

The basic helix-loop-helix protein BETA2/NeuroD activates transcription of the secretin gene and is essential for terminal differentiation of secretin-producing enteroendocrine cells. However, in heterodimeric complexes with its partner basic helix-loop-helix proteins, BETA2 does not appear to be a strong activator of transcription by itself. Mutational analysis of a proximal enhancer in the secretin gene identified several cis-acting elements in addition to the E-box binding site for BETA2. We identified by expression cloning the zinc finger protein RREB-1, also known to exist as a longer form, Finb, as the protein binding to one of the mutationally sensitive elements. Finb/RREB-1 lacks an intrinsic activation domain and by itself did not activate secretin gene transcription. Here we show that Finb/RREB-1 can associate with BETA2 to enhance its transcription-activating function. Both DNA binding and physical interaction of Finb/RREB-1 with BETA2 are required to potentiate transcription. Thus, Finb/RREB-1 does not function as a classical activator of transcription that recruits an activation domain to a DNA-protein complex. Finb/RREB-1 may be distinguished from coactivators, which increase transcription without sequence-specific DNA binding. We suggest that Finb/RREB-1 should be considered a potentiator of transcription, representing a distinct category of transcription-regulating proteins.

* Corresponding author. Mailing address: Division of Gastroenterology #218, New England Medical Center, 750 Washington St., Boston, MA 02111. Phone: (617) 636-8337. Fax: (617) 636-4207. E-mail: aleiter{at}lifespan.org.

{dagger} Present address: Department of Otolaryngology, Charles R. Drew University School of Medicine and Science, Los Angeles, CA 90059.

Molecular and Cellular Biology, January 2003, p. 259-271, Vol. 23, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.1.259-271.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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