1: Genes Dev. 2002 Aug 15;16(16):2097-107. 

Meis homeoproteins directly regulate Pax6 during vertebrate lens morphogenesis.

Zhang X, Friedman A, Heaney S, Purcell P, Maas RL.

Division of Genetics, Department of Medicine, Brigham & Women's Hospital and
Harvard Medical School, Boston, Massachusetts 02115, USA.

Pax6 is a pivotal regulator of eye development throughout Metazoa, but the
direct upstream regulators of vertebrate Pax6 expression are unknown. In
vertebrates, Pax6 is required for formation of the lens placode, an ectodermal
thickening that precedes lens development. Here we show that the Meis1 and Meis2
homeoproteins are direct regulators of Pax6 expression in prospective lens
ectoderm. In mice, Meis1 and Meis2 are developmentally expressed in a pattern
remarkably similar to Pax6 and their expression is Pax6-independent. Biochemical
and transgenic experiments reveal that Meis1 and Meis2 bind a specific sequence
in the Pax6 lens placode enhancer that is required for its activity.
Furthermore, Pax6 and Meis2 exhibit a strong genetic interaction in lens
development, and Pax6 expression is elevated in lenses of Meis2-overexpressing
transgenic mice. When expressed in embryonic lens ectoderm, dominant-negative
forms of Meis down-regulate endogenous Pax6. These results contrast with those
in Drosophila, where the single Meis homolog, Homothorax, has been shown to
negatively regulate eye formation. Therefore, despite the striking evolutionary
conservation of Pax6 function, Pax6 expression in the vertebrate lens is
uniquely regulated.

PMID: 12183364 [PubMed - indexed for MEDLINE]


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2: J Biol Chem. 2001 Jan 5;276(1):819-26. 

A set of Hox proteins interact with the Maf oncoprotein to inhibit its DNA
binding, transactivation, and transforming activities.

Kataoka K, Yoshitomo-Nakagawa K, Shioda S, Nishizawa M.

Department of Virology, Institute of Medical Science, University of Tokyo, 4-6-1
Shirokanedai, Minato-ku 108-8639, Tokyo, Japan. kkataoka@bio.titech.ac.jp

Maf oncoprotein is a basic-leucine zipper (bZip) type of transcriptional
activator. Since many transcription factors are known to form functional
complexes, we searched for proteins that interact with the DNA-binding domain of
Maf using the phage display method and identified two homeodomain-containing
proteins, Hoxd12 and MHox/Prx1/Phox1/Pmx1. Studies with mutants of Hox and Maf
proteins showed that they associate through their DNA-binding domains; the
homeodomain of Hox and the bZip domain of Maf, respectively. Reflecting the high
similarity of the bZip domain, all other Maf family members tested (c-/v-Maf,
MafB, MafK, MafF, and MafG) also associated with the Hox proteins. Pax6, whose
homeodomain is relatively similar to MHox, also could interact with Maf.
However, two other bZip oncoproteins, Fos and Jun, failed to associate with the
Hox proteins, while a distantly related Hox family member, Meis1, could not
interact with Maf. Through interactions with the bZip domain, the Hox proteins
inhibited the DNA binding activity of Maf, whereas the binding of Hox proteins
to their recognition sequences was not abrogated by Maf. We further showed that
coexpression of the Hox proteins repressed transcriptional activation and
transforming activity of Maf. These results suggested that the interaction of a
set of Hox proteins with Maf family members may interfere not only with their
oncogenicity but also with their physiological roles.

PMID: 11036080 [PubMed - indexed for MEDLINE]


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