I. Sanchezgarcia et al., THE CYSTEINE-RICH LIM DOMAINS INHIBIT DNA-BINDING BY THE ASSOCIATED HOMEODOMAIN IN ISL-1, EMBO journal, 12(11), 1993, pp. 4243-4250
Recently, a new class of homeobox genes has been identified, called LI
M-homeobox genes. These genes encode proteins which have two tandemly
repeated cysteine motifs, referred to as LIM domains, in addition to a
homeodomain. In addition, proteins with only LIM domains have been de
scribed but the function of the LIM domain is unknown. We have analyse
d the function of LIM domains using Isl-1 as a representative LIM-home
odomain protein. Employing protein prepared in bacterial cells, we sho
w that the presence of the LIM domain in Isl-1 inhibits binding of the
homeodomain to its DNA target. This in vitro inhibition can be releas
ed either by denaturation/renaturation of the protein or by truncation
of the LIM domains. A similar inhibition is observed in vivo using re
porter constructs. In addition we show that LIM domains in a chimeric
protein can inhibit binding of the Ubx homeodomain to its target. The
ability of LIM domains to inhibit DNA binding by the homeodomain provi
des a possible basis for negative regulation of LIM-homeodomain protei
ns in vivo.