Specific and conserved sequences in D. melanogaster and C. elegans lamins and histone H2A mediate the attachment of lamins to chromosomes.

The intimate association between nuclear lamins and chromatin is thought to regulate higher order chromatin organization. Previous studies have mapped a region between the rod domain and the Ig fold in the tail domain of Drosophila melanogaster lamin Dm0, which binds chromatin in vitro via the histone H2A/H2B dimer. This region contains an evolutionarily conserved nuclear localization signal (NLS) KRKR, and a sequence composed of the amino acids TRAT. Here we show that binding of lamin Dm0 to chromatin requires both NLS and TRAT sequences. Substituting either of the threonine residues in the TRAT sequence with negatively charged residues decreases the binding of lamin Dm0 to chromatin, indicating that this binding could be regulated by phosphorylation. Both lamin Dm0 and C. elegans Ce-lamin bind directly to histone H2A in vitro and this binding requires the NLS. The amino and carboxyl tail domains of histone H2A are each essential, but not sufficient, for binding to lamin Dm0; only a polypeptide containing both histone H2A tail domains binds efficiently to lamin Dm0. Taken together, these results suggest that specific residues in lamin Dm0 and histone H2A mediate the attachment of the nuclear lamina to chromosomes in vivo, which could have implications on the understanding of laminopathic diseases.