The immunoglobulin transcription factor-2B (ITF-2B) belongs to the basic helix-loop-helix (bHLH) family of transcription factors. it is ubiquitously expressed and plays a prominent role in the regulation of differentiation processes. Protein sequence alignment of the closely related bHLH transcription factors ITF-2B, HeLa E box protein (HITF4), and the E2A proteins E12 and E47 revealed the presence of a highly conserved protein domain. Functional analysis of this domain demonstrated that it plays an important role in repressing the transcriptional activity of the ITF-2B protein. Moreover, this domain comprises a self-contained transcriptional repressor whose activity depends on specific amino acid residues. (C) 2008 Elsevier Inc. All rights reserved.