RLIM inhibits functional activity of LIM homeodomain transcription factorsvia recruitment of the histone deacetylase complex

LIM domains(1) are required for both inhibitory effects on LIM homeodomain transcription factors and synergistic transcriptional activation events(1-4 ). The inhibitory actions of the LIM domain can often be overcome by the LI M co-regulator known as CLIM2, LDB1 and NLI (referred to hereafter as CLIM2 ; refs 2-4). The association of the CLIM cofactors with LIM domains does no t, however, improve the DNA-binding ability of LIM homeodomain proteins(4,5 ). suggesting the action of a LIM-associated inhibitor factor. Here we pres ent evidence that LIM domains are capable of binding a novel RING-H2 zinc-f inger protein, Rlim (for RING finger LIM domain-binding protein), which act s as a negative co-regulator via the recruitment of the Sin3A/histone deace tylase corepressor complex. A corepressor function of RLIM is also suggeste d by in vivo studies of chick wing development. Overexpression of the gene Rnf12, encoding Rlim, results in phenotypes similar to those observed after inhibition of the LIM homeodomain factor LHX2, which is required for the f ormation of distal structures along the proximodistal axis, or by overexpre ssion of dominant-negative CLIM1. We conclude that Rlim is a novel corepres sor that recruits histone deacetylase-containing complexes to the LIM domai n.