Format

Send to

Choose Destination
J Mol Biol. 2006 Jun 16;359(4):1137-49. Epub 2006 Apr 25.

Human transcription factors contain a high fraction of intrinsically disordered regions essential for transcriptional regulation.

Author information

1
Laboratory of Gene-Product Informatics, Center For Information Biology & DNA Data Bank of Japan, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.

Erratum in

  • J Mol Biol. 2006 Oct 13;363(1):309.

Abstract

Human transcriptional regulation factors, such as activators, repressors, and enhancer-binding factors are quite different from their prokaryotic counterparts in two respects: the average sequence in human is more than twice as long as that in prokaryotes, while the fraction of sequence aligned to domains of known structure is 31% in human transcription factors (TFs), less than half of that in bacterial TFs (72%). Intrinsically disordered (ID) regions were identified by a disorder-prediction program, and were found to be in good agreement with available experimental data. Analysis of 401 human TFs with experimental evidence from the Swiss-Prot database showed that as high as 49% of the entire sequence of human TFs is occupied by ID regions. More than half of the human TFs consist of a small DNA binding domain (DBD) and long ID regions frequently sandwiching unassigned regions. The remaining TFs have structural domains in addition to DBDs and ID regions. Experimental studies, particularly those with NMR, revealed that the transactivation domains in unbound TFs are usually unstructured, but become structured upon binding to their partners. The sequences of human and mouse TF orthologues are 90.5% identical despite a high incidence of ID regions, probably reflecting important functional roles played by ID regions. In general ID regions occupy a high fraction in TFs of eukaryotes, but not in prokaryotes. Implications of this dichotomy are discussed in connection with their functional roles in transcriptional regulation and evolution.

PMID:
16697407
DOI:
10.1016/j.jmb.2006.04.016
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center