[Frontiers in Bioscience 14, 1325-1336, January 1, 2009]

PML nuclear bodies as sites of epigenetic regulation

Dora Torok, Reagan W. Ching, David P. Bazett-Jones

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Structural integrity of PML NBs depends on chromatin
4. Specific gene loci associate with PML NBs
5. Some components of PML NBs affect genome integrity and gene expression
6. PML bodies contribute to the conservation of epigenetic information
7. A model for PML NB function in epigenetic regulation based on APL pathology
8. Possible role of PML NBs as epigenetic contributors to early tumorigenesis
9. Perspective
10. Acknowledgements
11. References

1. ABSTRACT

The protein-based core of a promyelocytic leukemia nuclear body (PML NB) accumulates numerous factors involved in many nuclear processes, including transcription and DNA repair. We suggest that these proteins could act on chromatin in the vicinity of the bodies. The physical dependence of PML NB structure on the integrity of the surrounding DNA implies a functional connection between the bodies and chromatin. Indeed, some genetic loci are non-randomly associated with PML NBs, indicating that nuclear bodies organize at specific loci, or are able to recruit specific genetic loci to their periphery. Since many of the factors that accumulate in PML NBs and PML-containing structures in acute promyelocytic leukemia cells are known histone methyltransferases, histone deacetylases or DNA methyltransferases, we suggest that PML NBs may have a role as epigenetic regulators. Down-regulation of normal PML protein, observed in a variety of cancers, may impair epigenetic regulation in early tumorigenesis, which ultimately leads to genetic instability and cellular transformation.