Domain-specific Interactions of Human HP1-type Chromodomain Proteins and Inner Nuclear Membrane Protein LBR

Abstract

HP1-type chromodomain proteins self-associate as well as interact with the inner nuclear membrane protein LBR (lamin B receptor) and transcriptional coactivators TIF1␣ and TIF1␤. The domains of these proteins that mediate their various interactions have not been entirely defined. HP1-type proteins are predicted by hydrophobic cluster analysis to consist of two homologous but distinct globular domains, corresponding to the chromodomain and chromo shadow domain, separated by a hinge region. We show here that the chromo shadow domain mediates the self-associations of HP1-type proteins and is also necessary for binding to LBR both in vitro and in the yeast two-hybrid assay. Hydrophobic cluster analysis also predicts that the nucleoplasmic amino-terminal portion of LBR contains two globular domains separated by a hinge region. The interactions of the LBR domains with an HP1-type protein were also analyzed by the yeast two-hybrid and in vitro binding assays, which 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 chromatin-lamina-membrane interface of the nuclear envelope.

Methylation of Lysine 9 in Histone H3 Directs Alternative Modes of Highly Dynamic Interaction of Heterochromatin Protein hHP1β with the Nucleosome

“…Swi6 showed, besides CSD dimerization, homo-interaction via the CD that was suggested to increase the specificity for H3K C 9me3-chromatin in a cooperative manner. We and others (6,13,47) did not find a similar multimerization behavior of hHP1␤ (supplemental Fig. 3, D and E).…”

Nuclear Envelope Irregularity Is Induced by RET/PTC During Interphase

“…7 Irregularity of NE shape, from any cause, could theoretically affect a number of cell physiologies. Nuclear lamina proteins are involved in determining replication competence 8 -14 and organizing transcription by binding to and segregating heterochromatin 15 (reviewed in 16 ). Consistent with a role in organizing transcription, large-scale localization of genes near the NE is associated with transcriptional silencing.…”

Inner nuclear membrane and signal transduction

“…Binding to fixed nuclear structures is responsible for the retention of proteins in the inner nuclear membrane Worman, 1993, 1995;Ellenberg et al, 1997;Ö stlund et al, 1999;Ohba et al, 2004]. Most of the characterized integral proteins of the inner nuclear membrane bind to nuclear lamins and/or chromatin components, example being lamin B receptor [Worman et al, 1988;Worman, 1994, 1996;Ye et al, 1997] and isoforms of lamina-associated polypeptide 2 [Foisner and Gerace, 1993]. Data obtained from a proteomics analysis of purified nuclear envelopes suggest that approximately 80 transmembrane proteins reside in the inner nuclear membrane of interphase cells [Schirmer et al, 2003].…”