DOMAIN-SPECIFIC INTERACTIONS OF HUMAN HP1-TYPE CHROMODOMAIN PROTEINS AND INNER NUCLEAR-MEMBRANE PROTEIN LBR

HP1-type chromodomain proteins self-associate as well as interact with the inner nuclear membrane protein LBR (lamin B receptor) and transcr iptional coactivators TIF1 alpha and TIF1 beta. The domains of these p roteins that mediate their various interactions have not been entirely defined. HP1-type proteins are predicted by hydrophobic cluster analy sis to consist of two homologous but distinct globular domains, corres ponding to the chromodomain and chrome shadow domain, separated by a h inge region. We show here that the chrome shadow domain mediates the s elf-associations of HP1-type proteins and is also necessary for bindin g to LBR both in vitro and in the yeast two-hybrid assay. Hydrophobic cluster analysis also predicts that the nucleoplasmic amino-terminal p ortion of LBR contains two globular domains separated by a hinge regio n. The interactions of the LBR domains with an HP1-type protein were a lso analyzed by the yeast two-hybrid and in vitro binding assays, whic h showed that a portion of the second globular domain is necessary for binding. The modular domain organization of HP1-type proteins and LBR can explain some of the diverse protein-protein interactions at the c hromatin-lamina-membrane interface of the nuclear envelope.