The homeoprotein Alx3 contains discrete functional domains and exhibits cell-specific and selective monomeric binding and transactivation.

The Journal of Biological Chemistry
B Perez-VillamilM Vallejo

Abstract

Alx3 is a paired class aristaless-like homeoprotein expressed during embryonic development. Transcriptional transactivation by aristaless-like proteins has been associated with cooperative dimerization upon binding to artificially generated DNA consensus sequences known as P3 sites, but natural target sites in genes regulated by Alx3 are unknown. We report the cloning of a cDNA encoding the rat homolog of Alx3, and we characterize the protein domains that are important for transactivation, dimerization, and binding to DNA. Two proline-rich domains located amino-terminal to the homeodomain (Pro1 and Pro2) are necessary for Alx3-dependent transactivation, whereas another one (Pro3) located in the carboxyl terminus is dispensable but contributes to enhance the magnitude of the response. We confirmed that transcriptional activity of Alx3 from a P3 site correlates with cooperative dimerization upon binding to DNA. However, Alx3 was found to bind selectively to non-P3-related TAAT-containing sites present in the promoter of the somatostatin gene in a specific manner that depends on the nuclear protein environment. Cell-specific transactivation elicited by Alx3 from these sites could not be predicted from in vitro DNA-binding experime...Continue Reading

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Citations

Dec 2, 2005·European Journal of Human Genetics : EJHG·Lampros A MavrogiannisAndrew O M Wilkie
Jul 12, 2011·Evolution & Development·Imelda M McGonnellTokiharu Takahashi
May 5, 2009·American Journal of Human Genetics·Stephen R F TwiggAndrew O M Wilkie
Dec 8, 2017·Journal of Human Genetics·Asmat UllahWasim Ahmad
Nov 5, 2016·Nature·Ricardo MallarinoHopi E Hoekstra
Jun 23, 2021·The Journal of Biological Chemistry·Jennifer Guerrero-SantoroCharles A Ettensohn

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