Determination of the minimal domains of Mix.3/Mixer required for endoderm development.

Abstract:

:The Mix/Bix family of Pax-like homeodomain transcription factors is expressed early in vertebrate development and play important roles in endoderm and mesoderm formation. Like other Pax-related homeodomain proteins, the Mix/Bix family binds DNA as monomers or dimers and dimerization is mediated by the homeodomain. While the Mix/Bix family shares extensive sequence homology within the DNA-binding homeodomain, ectopic expression of these proteins has profoundly different outcomes. Expression of Xenopus Mix.3/Mixer in explanted ectoderm results in endoderm differentiation, whereas Mix.1 expression does not. In this study we sought to define the domains of Mix.3/Mixer that are responsible for this endoderm inducing activity. We generated domain swap mutants between Mix.3/Mixer and Mix.1 and tested their ability to induce endoderm in explanted ectoderm. We demonstrate that the homeodomain and sixty-two amino acids in the carboxyl terminus are required to induce endoderm and that these domains must be on the same polypeptide and can not act in trans as a heterodimer. A Smad2 interaction motif in Mix.3/Mixer is involved in endoderm differentiation but is not essential. Thus, we have defined the regions of Mix.3/Mixer that confer endoderm-inducing activity. These studies reveal a novel co-operation between the homeodomain and a small domain in the carboxyl terminal region that is essential for Mix.3/Mixer function.

journal_name

Mech Dev

authors

Doherty JR,Zhu H,Kuliyev E,Mead PE

doi

10.1016/j.mod.2005.09.006

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

56-66

issue

1

eissn

0925-4773

issn

1872-6356

pii

S0925-4773(05)00163-2

journal_volume

123

pub_type

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