Replication initiation in mammalian cells: changing preferences.

Accurate duplication of genetic material is central to cell proliferation. In eukaryotes, S phase is tightly controlled during development. For example, initiation events occur at random sites in early embryos but later appear restricted to preferred DNA regions. Epigenetic changes depending on chromatin organization and/or availability of specific factors likely control origin choice. By using the dynamic molecular combing technology, coupled with specific labeling of neo-synthesized DNA and FISH, we recently demonstrated that the efficiency and spacing of initiation sites are still flexible in mammalian somatic cells, and strongly rely on nucleotide availability. In all conditions, initiation events appear confined to short AT-rich sequences previously identified as matrix attachment regions, which suggests a direct involvement of these features in origin specification. Functional relationships between matrix anchorage and origin selection are discussed.