Mechanisms of Epigenetic Inheritance Through Chromatin: Conclusion

In this chapter, we have described key components of the mechanisms of propagation of chromatin states through DNA replication. These include his-tone modifications and the responsible enzymes, histone chaperones, chromatin remodeling factors, RNA components, DNA methylation and the DNA replication machinery itself. Some of the known interactions suggest pathways by which histone modifications (for example, histone methylation at K9 of H3) recruit factors [e.g. HP1-SU(VAR)3-9 complexes] that propagate the same modification at adjacent sites. The segregation of parental histones to the daughter DNA strands during DNA replication may, therefore, mediate maintenance of the histone code of specific domains. One requirement for this scenario is that the dispersal of the parental histones to the new DNA strands has to be kept localized. One could imagine a molecular conveyor belt, possibly consisting of the DNA replication machinery itself, histone chaperones and remodeling factors, which secures the localized transmission of his-tones.

What may become obvious from this chapter is that while we know several components that are involved in epigenetic inheritance, we are far from understanding the mechanisms of this important aspect of biology. This is likely because, unlike the duplication of DNA, there is no single mechanism that mediates the duplication of chromatin states, but many different mechanisms exist, depending on chromatin domain, organism and function. This field will remain a major intellectual challenge for the foreseeable future.

Acknowledgements. Work in my laboratory was funded by Marie Curie Cancer Care. I wish to thank Sofia Aligianni, Ludmila Bozhenok, Sarah Elderkin, Margaret Grimaldi, Raymond Poot, Ana Neves Costa and Joao Ferreira for comments that improved the manuscript. Thanks also to Jim Kadonaga and Paul Kaufman for preprints of manuscripts.


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