Epigenetic control during embryogenesis

Division Of Basic Sciences - Nci

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Abstract

Our previous work had shown that LSH alters the composition of chromatin, namely the content of macroH2A, an important histone variant present in repressed chromatin. When LSH is recruited to a specific genomic location, we noticed increased deposition of macroH2A and upon depletion of LSH we found genome wide a reduction of the macroH2A content in chromatin. MacroH2A confers Using recombinant LSH we found that it interacts in vitro with macroH2A1 and macroH2A2, but not with the histone variant H2A.Z. Furthermore, wild type LSH, but not a catalytic mutant of LSH, was able to induce the exchange of H2A in a canonical nucleosome with macroH2A in vitro. The histone exchange reaction is specific for histone variant macroH2A, since LSH is not capable to incorporate H2A.Z. These findings define a previously unknown role for LSH in chromatin remodeling and identify a novel molecular mechanism for deposition of the histone variant macroH2A Our data suggest that LSH acts as a histone variant exchange factor. It shares this ability with the LSH homologue DDM1 in Arabidopsis thaliana. Like LSH, DDM1 is responsible for deposition of the heterochromatin associated histone variant H2A.W in plants, indicating a conserved function in evolution.