A CHROMATIN BINDING-SITE IN THE TAIL DOMAIN OF NUCLEAR LAMINS THAT INTERACTS WITH CORE HISTONES

Interaction of chromatin with the nuclear envelope and lamina is thoug ht to help determine higher order chromosome organization in the inter phase nucleus. Previous studies have shown that nuclear lamins bind ch romatin directly. Here we have localized a chromatin binding site to t he carboxyl-terminal tail domains of both A- and B-type mammalian lami ns, and have characterized the biochemical properties of this binding in detail. Recombinant glutathione-S-transferase fusion proteins conta ining the tail domains of mammalian lamins C, B-1, and B-2 were analyz ed for their ability to associate with rat liver chromatin fragments i mmobilized on microtiter plate wells. We found that all three lamin ta ils specifically bind to chromatin with apparent K(d)s of 120-300 nM. By examining a series of deletion mutants, we have mapped the chromati n binding region of the lamin C tail to amino acids 396-430, a segment immediately adjacent to the rod domain. Furthermore, by analysis of c hromatin subfractions, we found that core histones constitute the prin cipal chromatin binding component for the lamin C tail. Through cooper ativity, this lamin-histone interaction could be involved in specifyin g the high avidity attachment of chromatin to the nuclear envelope in vivo.