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The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK
Latency Abstract 7
MULTIPLE DOMAINS CONTRIBUTE TO THE ASSOCIATION OF LANA WITH HOST
CHROMATIN COMPONENTS
Ryo Nasu, Satoko Matsumura, Naoko Tanese and Angus Wilson
Department of Microbiology & NYU Cancer Institute, New York University School of
Medicine, New York, NY 10016, USA
Abstract
The latency-associated nuclear antigen (LANA, LANA1, LNA1) encoded by ORF73 is
expressed in all KSHV infected cells and performs a variety of functions associated with
maintenance of the viral genome and proliferation of the infected host cell. As its name
indicates, LANA accumulates in the nucleus where it is associated with host chromosomes
throughout the cell cycle. Direct interactions with a number of chromatin components
have been described but the functional significance of these interactions is not fully
understood. We have focused on the association of LANA with methyl-CpG binding
protein 2 (MeCP2) and core histones. Evidence will be presented showing that both the
N- and C-terminal domains of LANA contribute to interaction with MeCP2 and this can
direct LANA to regions of pericentric heterochromatin. Localization is dependent on the
methyl-CpG binding (MBD) and adjacent trans-repression (TRD) domains of MeCP2. The
chromatin binding motif (CBM) at the extreme N-terminus of LANA (residues 5-11)
influences subcellular localization but is not strictly required for MeCP2 binding. Instead,
the CBM recognizes the four histones that form the nucleosome core. In addition to
interactions with histones H2A/H2B previously described by the Kaye and Luger
laboratories, we will present evidence for additional interactions with histones H3 and H4.
Sedimentation studies employing recombinant proteins show that the LANA CBM is
capable of assembling isolated nucleosomes into compacted structures that may serve to
regulate host and viral gene expression.
Presenting author Email: wilsoa02@med.nyu.edu
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