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The Mi-2/NuRD complex associates with pericentromeric heterochromatin during S phase in rapidly proliferating lymphoid cells

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Abstract

Chromosomal replication results in the duplication not only of DNA sequence but also of the patterns of histone modification, DNA methylation, and nucleoprotein structure that constitute epigenetic information. Pericentromeric heterochromatin in human cells is characterized by unique patterns of histone and DNA modification. Here, we describe association of the Mi-2/NuRD complex with specific segments of pericentromeric heterochromatin consisting of Satellite II/III DNA located on human chromosomes 1, 9, and 16 in some but not all cell types. This association is linked in part to DNA replication and chromatin assembly and may suggest a role in these processes. Mi-2/NuRD accumulation is independent of Polycomb association and is characterized by a unique pattern of histone modification. We propose that Mi-2/NuRD constitutes an enzymatic component of a pathway for assembly and maturation of chromatin utilized by rapidly proliferating lymphoid cells for replication of constitutive heterochromatin.

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Acknowledgements

We thank Dr. Huntington Willard (Duke University), Dr. Weidong Wang (National Institute of Aging), Dr. Judd Rice (University of Southern California), Dr. Stephen Smale (UCLA), and Dr. Maureen Powers (Emory University) for the generous gift of antibodies used in this study. We are grateful to Dr. Beth Sullivan for excellent suggestions and to Jeff Reece and the NIEHS Confocal Microscopy Center for assistance with confocal imaging. This manuscript was substantially improved by critical comments from Dr. Karen Adelman, Dr. Melanie Erlich, and Dr. Harriet Kinyamu. We gratefully acknowledge technical assistance from Dr. Anne Lai and Dr. Jennifer Sims in the isolation and analysis of primary B lymphocytes. We thank the various members of the Wade, Adelman, and Archer laboratories for useful discussions during the course of this work. This work was supported in part by the Intramural Research Program of the National Institute of Environmental Health Sciences (Project number Z01ES101965), NIH (PW), and by grants from the National Institutes of Health (GM073120 to BPC, DK60647 to DLJ).

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Authors and Affiliations

  1. Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA

    Lisa Helbling Chadwick & Paul A. Wade

  2. Institute for Genome Sciences and Policy, Duke University, Durham, NC, 27710, USA

    Brian P. Chadwick

  3. Department of Cell Biology, Duke University, Durham, NC, 27710, USA

    Brian P. Chadwick

  4. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA

    David L. Jaye

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  1. Lisa Helbling Chadwick
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Correspondence to Paul A. Wade.

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Communicated by G. Almouzni.

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Supplementary Fig. 1

Localization of additional Mi-2/NuRD subunits relative to MTA3 in GC B-cell-like lines. Ramos cells were immunostained with antibodies against MTA3 (green) and either MTA1 or MTA2 (red). (79.1 kb)

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Helbling Chadwick, L., Chadwick, B.P., Jaye, D.L. et al. The Mi-2/NuRD complex associates with pericentromeric heterochromatin during S phase in rapidly proliferating lymphoid cells. Chromosoma 118, 445–457 (2009). https://doi.org/10.1007/s00412-009-0207-7

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