The flexibility of a homeodomain transcription factor heterodimer and its allosteric regulation by DNA binding

FEBS Journal ◽  
2016 ◽  
Vol 283 (16) ◽  
pp. 3134-3154 ◽  
Author(s):  
Lisa Mathiasen ◽  
Erica Valentini ◽  
Stephane Boivin ◽  
Angela Cattaneo ◽  
Francesco Blasi ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Allosteric Regulation ◽  
Homeodomain Transcription Factor

scholarly journals Discovery, optimization and validation of an optimal DNA-binding sequence for the Six1 homeodomain transcription factor

2012 ◽  
Vol 40 (17) ◽  
pp. 8227-8239 ◽  
Author(s):  
Yubing Liu ◽  
Soumyadeep Nandi ◽  
André Martel ◽  
Alen Antoun ◽  
Ilya Ioshikhes ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Homeodomain Transcription Factor ◽  
Binding Sequence

scholarly journals Paired-Homeodomain Transcription Factor PAX4 Acts as a Transcriptional Repressor in Early Pancreatic Development

1999 ◽  
Vol 19 (12) ◽  
pp. 8272-8280 ◽  
Author(s):  
Stuart B. Smith ◽  
Hooi C. Ee ◽  
Jennifer R. Conners ◽  
Michael S. German
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
Dna Binding ◽  
Binding Site ◽  
Cell Line ◽  
Transcriptional Repressor ◽  
Paired Domain ◽  
Β Cell ◽  
Pancreatic Development ◽  
Homeodomain Transcription Factor

ABSTRACT The paired-homeodomain transcription factor PAX4 is expressed in the developing pancreas and along with PAX6 is required for normal development of the endocrine cells. In the absence of PAX4, the numbers of insulin-producing β cells and somatostatin-producing δ cells are drastically reduced, while the numbers of glucagon-producing α cells are increased. To gain insight into PAX4 function, we cloned a full-length Pax4 cDNA from a β-cell cDNA library and identified a bipartite consensus DNA binding sequence consisting of a homeodomain binding site separated from a paired domain binding site by 15 nucleotides. The paired half of this consensus sequence has similarities to the PAX6 paired domain consensus binding site, and the two proteins bind to common sequences in several islet genes, although with different relative affinities. When expressed in an α-cell line, PAX4 represses transcription through the glucagon or insulin promoters or through an isolated PAX4 binding site. This repression is not simply due to competition with the PAX6 transcriptional activator for the same binding site, since PAX4 fused to the unrelated yeast GAL4 DNA binding domain also represses transcription through the GAL4 binding site in the α-cell line and to a lesser degree in β-cell lines and NIH 3T3 cells. Repressor activity maps to more than one domain within the molecule, although the homeodomain and carboxyl terminus give the strongest repression. PAX4 transcriptional regulation apparently plays a role only early in islet development, since Pax4 mRNA as determined by reverse transcriptase PCR peaks at embryonic day 13.5 in the fetal mouse pancreas and is undetectable in adult islets. In summary, PAX4 can function as a transcriptional repressor and is expressed early in pancreatic development, which may allow it to suppress α-cell differentiation and permit β-cell differentiation.

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