DNA binding and gene activation properties of the Nmp4 nuclear matrix transcription factors

Kitti Torrungruang, Marta Alvarez, Rita Shah, Jude E. Onyia, Simon Rhodes, Joseph Bidwell

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Splice variants of the Nmp4 gene include nuclear matrix transcription factors that regulate the type I collagen α1(I) polypeptide chain (COL1A1) promoter and several matrix metalloproteinase (MMP) genes. To date, these are the only Cys2His2 zinc finger proteins known to bind within the minor groove of homopolymeric (dA·dT) DNA. Nmp4 isoforms contain from 5 to 8 Cys2His2 zinc fingers, an SH3-binding domain that overlaps with a putative AT-hook and a polyglutamine-alanine repeat (poly(QA)). To determine the mechanistic significance of Cys2His2 zinc finger association with this unusual consensus DNA binding element, we identified the Nmp4 DNA-binding and transcriptional activation domains. Zinc fingers 2, 3, and 6 mediated association with the homopolymeric (dA·dT) COL1A1/MMP DNA consensus element. The N terminus of the Nmp4 protein exhibited a strong trans-activation capacity when fused to the GAL4 DNA-binding domain, but this activity was masked within the context of the full-length Nmp4-GAL4 DNA-binding domain chimera. However, upon binding to the COL1A1/MMP homopolymeric (dA·dT) element, the native Nmp4 protein up-regulated transcription, and the poly(QA) domain acquired a significant role in trans-activation. We propose that allosteric effects induced upon zinc finger association with the homopolymeric (dA·dT) minor groove confer context-specific functionality to this unusual family of Cys2His2 transcription factors.

Original languageEnglish
Pages (from-to)16153-16159
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number18
DOIs
StatePublished - May 3 2002

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Nuclear Matrix
Zinc Fingers
Transcriptional Activation
Transcription Factors
Genes
Chemical activation
Zinc
DNA
Matrix Metalloproteinases
Association reactions
AT-Hook Motifs
Proteins
src Homology Domains
Hooks
Transcription
Collagen Type I
Alanine
Protein Isoforms
Peptides

ASJC Scopus subject areas

  • Biochemistry

Cite this

DNA binding and gene activation properties of the Nmp4 nuclear matrix transcription factors. / Torrungruang, Kitti; Alvarez, Marta; Shah, Rita; Onyia, Jude E.; Rhodes, Simon; Bidwell, Joseph.

In: Journal of Biological Chemistry, Vol. 277, No. 18, 03.05.2002, p. 16153-16159.

Research output: Contribution to journalArticle

Torrungruang, Kitti ; Alvarez, Marta ; Shah, Rita ; Onyia, Jude E. ; Rhodes, Simon ; Bidwell, Joseph. / DNA binding and gene activation properties of the Nmp4 nuclear matrix transcription factors. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 18. pp. 16153-16159.
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