RGD Reference Report - Critical Roles of the LIM Domains of Lhx3 in Recruiting Coactivators to the Motor Neuron-Specifying Isl1-Lhx3 Complex. - Rat Genome Database

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Critical Roles of the LIM Domains of Lhx3 in Recruiting Coactivators to the Motor Neuron-Specifying Isl1-Lhx3 Complex.

Authors: Seo, So Yeon  Lee, Bora  Lee, Seunghee 
Citation: Seo SY, etal., Mol Cell Biol. 2015 Oct;35(20):3579-89. doi: 10.1128/MCB.00335-15. Epub 2015 Aug 10.
RGD ID: 243065122
Pubmed: PMID:26260513   (View Abstract at PubMed)
PMCID: PMC4573714   (View Article at PubMed Central)
DOI: DOI:10.1128/MCB.00335-15   (Journal Full-text)

During spinal cord development, the LIM domains of the LIM homeodomain factor Lhx3 bind to either the LIM cofactor nuclear LIM interactor (NLI) or another LIM homeodomain factor, Isl1, assembling the tetrameric V2 interneuron-specifying Lhx3 complex (2NLI:2Lhx3) or the hexameric motor neuron-specifying Isl1-Lhx3 complex (2NLI:2Isl1:2Lhx3). However, the detailed molecular basis by which the Lhx3-LIM domains contribute to motor neuron specification still remains poorly understood. Here, we show that the Lhx3-LIM domains are essential for recruiting transcriptional coactivators to the Isl1-Lhx3 complex. Using a yeast genetic screening system, we identify Lhx3 point mutants that bind to NLI but not Isl1. Accordingly, these mutants fail to assemble the Isl1-Lhx3 complex. However, their interaction with coactivators is relatively intact, and they are fully functional in the Lhx3 complex and V2 interneuron specification. Interestingly, when these Lhx3 mutants are directly fused to Isl1, their transcriptional activity in the Isl1-Lhx3 complex is restored. We further show that this restoration reflects an unexpected role of the Lhx3-LIM domains, likely together with Isl1, to form an interaction interface for coactivators. Our results suggest that the Lhx3-LIM domains play critical roles in transactivation of the Isl1-Lhx3 complex by not only directing the assembly of the Isl1-Lhx3 complex but also recruiting coactivators to the complex.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Isl1RatLIM domain binding  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Isl1  (ISL LIM homeobox 1)

Additional Information