Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity

Yanfen Hu, Bernhard Lüscher, Arie Adinon, Nicolas Mermod, Robert Tjian

Research output: Contribution to journalArticle

219 Citations (Scopus)

Abstract

Enhancer binding protein AP-4 is a transcription factor that activates both viral and cellular genes by binding to the symmetrical DNA sequence, CAGCTG. Here, we report the molecular cloning and characterization of human AP-4 cDNAs. The deduced amino acid sequence reveals that AP-4 is a helix-loop-helix (HLH) protein. Like other members of this family, the AP-4 HLH motif and the adjacent basic domain are necessary and sufficient to confer site-specific DNA binding. However, unlike other HLH proteins, AP-4 also contains two additional protein dimerization motifs consisting of leucine repeat elements LR1 and LR2. The analysis of various deletion and point mutants for their ability to dimerize in the presence or absence of DNA reveals several unusual features. Although the HLH basic region is sufficient for DNA recognition and binding, dimer formation between different truncated versions of AP-4 in solution requires an intact LR1 or LR2 domain. AP-4 is unable to form heterodimers with other helix-loop-helix family members such as the immunoglobulin enhancer binding factor, E12. In contrast, an AP-4 derivative, ΔC222, which lacks LR1 and LR2 but retains an intact HLH, can form heterodimers with E12. Moreover, AP-4 molecules containing LR2 or LR1 are unable to form mixed dinners with carboxy-terminally truncated AP-4 molecules such as ΔC222, but retain the ability to form complexes with longer versions of AP-4 that contain LR1 and/or LR2. Our findings strongly suggest that AP-4 contains multiple protein-protein interfaces that function to promote homodimer formation and restrict heterocomplexes. These findings provide a mechanism by which different members of the helix-loop-helix family of transcription factors can form functional dimers in a specific fashion with their appropriate partners to control transcriptional networks during cellular differentiation.

Original languageEnglish (US)
Pages (from-to)1741-1752
Number of pages12
JournalGenes and Development
Volume4
Issue number10
StatePublished - 1990
Externally publishedYes

Fingerprint

Dimerization
Aptitude
DNA
Helix-Loop-Helix Motifs
Proteins
Transcription Factors
Protein Multimerization
Amino Acid Motifs
Viral Genes
Gene Regulatory Networks
Molecular Cloning
Leucine
Meals
Amino Acid Sequence
Complementary DNA
enhancer-binding protein AP-4

Keywords

  • AP-4
  • Dimerization specificity
  • Helix-loop-helix
  • Leucine repeat

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Hu, Y., Lüscher, B., Adinon, A., Mermod, N., & Tjian, R. (1990). Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. Genes and Development, 4(10), 1741-1752.

Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. / Hu, Yanfen; Lüscher, Bernhard; Adinon, Arie; Mermod, Nicolas; Tjian, Robert.

In: Genes and Development, Vol. 4, No. 10, 1990, p. 1741-1752.

Research output: Contribution to journalArticle

Hu, Y, Lüscher, B, Adinon, A, Mermod, N & Tjian, R 1990, 'Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity', Genes and Development, vol. 4, no. 10, pp. 1741-1752.
Hu, Yanfen ; Lüscher, Bernhard ; Adinon, Arie ; Mermod, Nicolas ; Tjian, Robert. / Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. In: Genes and Development. 1990 ; Vol. 4, No. 10. pp. 1741-1752.
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