1: J Biol Chem. 2004 Jul 16;279(29):30287-97. Epub 2004 May 11. 

TALE homeodomain proteins regulate gonadotropin-releasing hormone gene
expression independently and via interactions with Oct-1.

Rave-Harel N, Givens ML, Nelson SB, Duong HA, Coss D, Clark ME, Hall SB, Kamps
MP, Mellon PL.

Department of Reproductive Medicine, School of Medicine, University of
California, San Diego, La Jolla, California 92903, USA.

Gonadotropin-releasing hormone (GnRH) is the central regulator of reproductive
function. Expression of the GnRH gene is confined to a rare population of
neurons scattered throughout the hypothalamus. Restricted expression of the rat
GnRH gene is driven by a multicomponent enhancer and an evolutionarily conserved
promoter. Oct-1, a ubiquitous POU homeodomain transcription factor, was
identified as an essential factor regulating GnRH transcription in the GT1-7
hypothalamic neuronal cell line. In this study, we conducted a two-hybrid
interaction screen in yeast using a GT1-7 cDNA library to search for specific
Oct-1 cofactors. Using this approach, we isolated Pbx1b, a TALE homeodomain
transcription factor that specifically associates with Oct-1. We show that
heterodimers containing Pbx/Prep1 or Pbx/Meis1 TALE homeodomain proteins bind to
four functional elements within the GnRH regulatory region, each in close
proximity to an Oct-1-binding site. Cotransfection experiments indicate that
TALE proteins are essential for GnRH promoter activity in the GT1-7 cells.
Moreover, Pbx1 and Oct-1, as well as Prep1 and Oct-1, form functional complexes
that enhance GnRH gene expression. Finally, Pbx1 is expressed in GnRH neurons in
embryonic as well as mature mice, suggesting that the associations between TALE
homeodomain proteins and Oct-1 regulate neuron-specific expression of the GnRH
gene in vivo.

PMID: 15138251 [PubMed - indexed for MEDLINE]


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2: EMBO J. 1998 Mar 2;17(5):1423-33. 

Prep1, a novel functional partner of Pbx proteins.

Berthelsen J, Zappavigna V, Mavilio F, Blasi F.

Dipartimento di Genetica e Biologia dei Microrganismi dell'Universita, DIBIT,
H.S. Raffaele, via Olgettina 58, 20132, Milan, Italy.

The human transcription factor, UEF3, is important in regulating the activity of
the urokinase plasminogen activator (uPA) gene enhancer. The UEF3 DNA target
site is a regulatory element in the promoters of several growth factor and
protease genes. We reported previously that purified UEF3 is a complex of
several subunits. In this paper we report the cloning of the cDNA of one of the
subunits which encodes for a novel human homeodomain protein, which we have
termed Prep1. The Prep1 homeodomain belongs to the TALE class of homeodomains,
is most closely related to those of the TGIF and Meis1 proteins, and like these,
recognizes a TGACAG motif. We further identify the other UEF3 subunit as a
member of the Pbx protein family. Unlike other proteins known to interact with
Pbx, Prep1 forms a stable complex with Pbx independent of DNA binding.
Heterodimerization of Prep1 and Pbx results in a strong DNA binding affinity
towards the TGACAG target site of the uPA promoter. Overall, these data indicate
that Prep1 is a stable intracellular partner of Pbx in vivo.

PMID: 9482739 [PubMed - indexed for MEDLINE]


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