Comparison of TFII-I gene family members deleted in Williams-Beuren syndrome

Protein Sci. 2004 Oct;13(10):2588-99. doi: 10.1110/ps.04747604.


Williams-Beuren syndrome (WBS) is a neurological disorder resulting from a microdeletion, typically 1.5 megabases in size, at 7q11.23. Atypical patients implicate genes at the telomeric end of this multigene deletion as the main candidates for the pathology of WBS in particular the unequal cognitive profile associated with the condition. We recently identified a gene (GTF2IRD2) that shares homology with other members of a unique family of transcription factors (TFII-I family), which reside in the critical telomeric region. Using bioinformatics tools this study focuses on the detailed assessment of this gene family, concentrating on their characteristic structural components such as the leucine zipper (LZ) and I-repeat elements, in an attempt to identify features that could aid functional predictions. Phylogenetic analysis identified distinct I-repeat clades shared between family members. Linking functional data to one such clade has implicated them in DNA binding. The identification of PEST, synergy control motifs, and sumoylation sites common to all family members suggest a shared mechanism regulating the stability and transcriptional activity of these factors. In addition, the identification/isolation of short truncated isoforms for each TFII-I family member implies a mode of self-regulation. The exceptionally high identity shared between GTF2I and GTF2IRD2, suggests that heterodimers as well as homodimers are possible, and indicates overlapping functions between their respective short isoforms. Such cross-reactivity between GTF2I and GTF2IRD2 short isoforms might have been the evolutionary driving force for the 7q11.23 chromosomal rearrangement not present in the syntenic region in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Chromosomes, Human, Pair 7 / genetics
  • Computational Biology
  • Exons / genetics
  • Gene Deletion*
  • Humans
  • Leucine Zippers / genetics
  • Molecular Sequence Data
  • Muscle Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Phylogeny
  • Protein Isoforms / genetics
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Trans-Activators / genetics*
  • Transcription Factors, TFII / genetics*
  • Transcription Factors, TFIII
  • Williams Syndrome / genetics*


  • GTF2I protein, human
  • GTF2IRD1 protein, human
  • GTF2IRD2 protein, human
  • Muscle Proteins
  • Nuclear Proteins
  • Protein Isoforms
  • Trans-Activators
  • Transcription Factors, TFII
  • Transcription Factors, TFIII

Associated data

  • GENBANK/AY312851
  • GENBANK/AY336979
  • GENBANK/AY336980
  • GENBANK/AY336981