Involvement of Linker Histones in the Regulation of Replication Timing

In eukaryotic cells, genomic DNA is associated with proteins to form chromatin, wherein the basic subunit is the nucleosome (van Holde 1989; Luger et al. 1997). The histones that compose the nucleosome can undergo posttranslational modifications, which are believed to generate an epigenetic code involved in chromatin activity regulation (Jenuwein and Allis 2001). Like other chromatin activities, replication has been correlated with histone modification. However unlike other activities, such as transcription or repair, wherein core histones are specifically modified, the histone posttranslational modifications that have been shown involved in replication regulation also interest the linker histone. While the linker histone has been shown mobile within the nucleus, the way the linker histone can be associated with replication timing regulation is of general interest. The present chapter reviews structural features of chromatin and the function of linker histone in higher order of chromatin. As replication implies the accessibility of the replication machinery to DNA, the modalities that are associated with a release of compact structure involving the linker histone will be discussed as well as the function of protein kinases in this process. This will lead to a model proposing how chromatin structure can switch from a non-permissive structure to a replication competent chromatin structure. Finally, with regard to our knowledge of chromatin replication requirements and the mobility of chromatin structures, the concluding remarks point out concerns that are not yet addressed in the timely regulated process of replication.