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PMID: 7957066 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending.

The EMBO journal ·Vol. 13 ·No. 20 ·1994-10-17 ·Pages 5002-12

Pierrou S, Hellqvist M, Samuelsson L, Enerbäck S, Carlsson P

Abstract

The forkhead domain is a monomeric DNA binding motif that defines a rapidly growing family of eukaryotic transcriptional regulators. Genetic and biochemical data suggest a central role in embryonic development for genes encoding forkhead proteins. We have used PCR and low stringency hybridization to isolate clones from human cDNA and genomic libraries that represent seven novel forkhead genes, freac-1 to freac-7. The spatial patterns of expression for the seven freac genes range from specific for a single tissue to nearly ubiquitous. The DNA binding specificities of four of the FREAC proteins were determined by selection of binding sites from random sequence oligonucleotides. The binding sites for all four FREAC proteins share a core sequence, RTAAAYA, but differ in the positions flanking the core. Domain swaps between two FREAC proteins identified two subregions within the forkhead domain as responsible for creating differences in DNA binding specificity. Applying a circular permutation assay, we show that binding of FREAC proteins to their cognate sites results in bending of the DNA at an angle of 80-90 degrees.

Related Genes
freac
MeSH Terms
Amino Acid Sequence Base Sequence Binding Sites Cloning, Molecular DNA-Binding Proteins/genetics,metabolism Forkhead Transcription Factors Humans Models, Molecular Molecular Sequence Data Nuclear Proteins/genetics,metabolism Nucleic Acid Conformation Sequence Homology, Amino Acid Tissue Distribution Transcription Factors/genetics,metabolism
Chemicals
DNA-Binding Proteins Forkhead Transcription Factors Nuclear Proteins Transcription Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Pierrou S
Department of Molecular Biology, Göteborg University, Sweden.
Hellqvist M
Samuelsson L
Enerbäck S
Carlsson P
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52 references, click to expand
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-10-17
Pages
5002-12
Language
English
Region
England
NLM ID
8208664
PMCID
PMC395442
Subset
IM
Databases
GENBANK
U13219, U13220, U13221, U13222, U13223, U13224, U13225
External Links
PubMed source PMC Full Text View journal details
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