Intrinsic disorder in transcription factors

Jiangang Liu, Narayanan B. Perumal, Christopher J. Oldfield, Eric W. Su, Vladimir N. Uversky, A. Dunker

Research output: Contribution to journalArticle

347 Citations (Scopus)

Abstract

Intrinsic disorder (ID) is highly abundant in eukaryotes, which reflect the greater need for disorder-associated signaling and transcriptional regulation in nucleated cells. Although several well-characterized examples of intrinsically disordered proteins in transcriptional regulation have been reported, no systematic analysis has been reported so far. To test for the general prevalence of intrinsic disorder in transcriptional regulation, we used the predictor of natural disorder regions (PONDR) to analyze the abundance of intrinsic disorder in three transcription factor datasets and two control sets. This analysis revealed that from 94.13 to 82.63% of transcription factors possess extended regions of intrinsic disorder, relative to 54.51 and 18.64% of the proteins in two control datasets, which indicates the significant prevalence of intrinsic disorder in transcription factors. This propensity of transcription factors to intrinsic disorder was confirmed by cumulative distribution function analysis and charge-hydropathy plots. The amino acid composition analysis showed that all three transcription factor datasets were substantially depleted in order-promoting residues and significantly enriched in disorder-promoting residues. Our analysis of the distribution of disorder within the transcription factor datasets revealed that (a) the AT-hooks and basic regions of transcription factor DNA-binding domains are highly disordered; (b) the degree of disorder in transcription factor activation regions is much higher than that in DNA-binding domains; (c) the degree of disorder is significantly higher in eukaryotic transcription factors than in prokaryotic transcription factors; and (d) the level of α-MoRF (molecular recognition feature) prediction is much higher in transcription factors. Overall, our data reflected the fact that eukaryotes with well-developed gene transcription machinery require transcription factor flexibility to be more efficient.

Original languageEnglish
Pages (from-to)6873-6888
Number of pages16
JournalBiochemistry
Volume45
Issue number22
DOIs
StatePublished - Jun 6 2006

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Transcription Factors
Eukaryota
AT-Hook Motifs
Intrinsically Disordered Proteins
Molecular recognition
Hooks
DNA
Transcription
Transcriptional Activation
Machinery
Distribution functions
Genes
Chemical activation
Amino Acids
Datasets
Chemical analysis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Liu, J., Perumal, N. B., Oldfield, C. J., Su, E. W., Uversky, V. N., & Dunker, A. (2006). Intrinsic disorder in transcription factors. Biochemistry, 45(22), 6873-6888. https://doi.org/10.1021/bi0602718

Intrinsic disorder in transcription factors. / Liu, Jiangang; Perumal, Narayanan B.; Oldfield, Christopher J.; Su, Eric W.; Uversky, Vladimir N.; Dunker, A.

In: Biochemistry, Vol. 45, No. 22, 06.06.2006, p. 6873-6888.

Research output: Contribution to journalArticle

Liu, J, Perumal, NB, Oldfield, CJ, Su, EW, Uversky, VN & Dunker, A 2006, 'Intrinsic disorder in transcription factors', Biochemistry, vol. 45, no. 22, pp. 6873-6888. https://doi.org/10.1021/bi0602718
Liu J, Perumal NB, Oldfield CJ, Su EW, Uversky VN, Dunker A. Intrinsic disorder in transcription factors. Biochemistry. 2006 Jun 6;45(22):6873-6888. https://doi.org/10.1021/bi0602718
Liu, Jiangang ; Perumal, Narayanan B. ; Oldfield, Christopher J. ; Su, Eric W. ; Uversky, Vladimir N. ; Dunker, A. / Intrinsic disorder in transcription factors. In: Biochemistry. 2006 ; Vol. 45, No. 22. pp. 6873-6888.
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