FIG. 8.

Schematics of possible multivalent interactions among LANA, core histones, and MeCP2. (i) Evidence suggests that LANA may be folded such that LANA_N, which includes the CBM, is brought into proximity to LANA_C. For simplicity, only one molecule of LANA is shown; however, LANA most likely exists as a stable dimer. (ii) Engagement of the CBM with a nucleosome may alter the conformation, making the C-terminal domain more accessible to secondary interactions. (iii) Interaction of LANA_C with MeCP2 forms a relatively stable complex mediated by contacts between the CBM and the nucleosome core (a) and DNA and the MeCP2 MBD (b). As a consequence of these multivalent interactions, LANA accumulates with MeCP2 at the chromocenters. (iv) In the absence of the CBM, the LANA protein (LANA_FLΔ22) shows reduced retention at the chromocenters. This may occur because the deletion alters the accessibility of the LANA_C domain or increases the rate at which LANA exchanges with other interaction partners located in more euchromatic regions of the genome.