5-methyl-cytosine binding proteins loop DNA under nanoconfinement

Methyl-binding domain proteins are a family of proteins that possess a domain to selectively bind 5-methyl cytosine in an CpG context. Members of the family interact with other proteins to modulate DNA packing. Stretching of DNA-protein complexes in nanofluidic channels with a cross-section of a few persistence lengths allows us to probe the degree of packing by such proteins. Herewe demonstrate compaction by MeCP2 while MBD2 does not affect DNA configuration. By using atomic force microscopy (AFM), we determined that the likely mechanism for compaction by MeCP2 is the formation of bridges between distant DNA stretches and the formation of loops. We discuss the potential of both proteins for epigenetic mapping.