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Developmental regulation of Suz12 localization

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Abstract

Chromatin modifications are among the epigenetic alterations essential for genetic reprogramming during development. The Polycomb group (PcG) gene family mediates chromatin modifications that contribute to developmentally regulated transcriptional silencing. Trimethylation of histone H3 on lysine 27, mediated by a PcG protein complex consisting of Eed, Ezh2, and Suz12, is integral in differentiation, stem cell self-renewal, and tumorigenesis. Eed and Ezh2 are also implicated in the developmentally regulated silencing of the inactive X chromosome, as they are transiently enriched on the inactive X chromosome when X chromosome silencing is initiated. Here we analyze the dynamic localization of Suz12 during cellular differentiation and X-inactivation. Though Suz12 is a requisite member of the Eed/Ezh2 complexes, we found that Suz12 exhibits a notable difference from Ezh2 and Eed: while Ezh2 and Eed levels decrease during stem cell differentiation, Suz12 levels remain constant. Despite the differential regulation in abundance of Suz12 and Eed/Ezh2, Suz12 is also transiently enriched on the Xi during early stages of X-inactivation, and this accumulation is Xist RNA dependent. These results suggest that Suz12 may have a function that is not mediated by its association with Eed and Ezh2, and that this additional function is not involved in the regulation of X-inactivation.

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Acknowledgements

We thank the members of the Panning Lab, Brian Biehs, and Uta Grieshammer for their critical reading of the manuscript. We are grateful to Susanna Mlynarczyk-Evans for assistance with cell culture and Hannah Cohen for generating the human XIST RNA probe. B.P. is a Pew Scholar and is funded by NIH and by grants from the Howard Hughes Medical Institute and the Sandler Family Foundation. K.P. was a Fellow of the Life Sciences Research foundation and is currently a Special Fellow of the Leukemia and Lymphoma Society. D.A.N. is a recipient of the University of California, Office of the President Dissertation Year fellowship. K.A.W. is an A.R.C.S. foundation fellow. C.C.C. is a recipient of a National Sciences Foundation predoctoral fellowship.

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, University of California, San Francisco, CA, 94143, USA

    Cecile C. de la Cruz, Kathleen A. Worringer, Dmitri A. Nusinow & Barbara Panning

  2. Department of Biochemistry and Biophysics, The University of North Carolina, Chapel Hill, NC, 27599, USA

    Jia Fang & Yi Zhang

  3. Whitehead Institute for Biomedical Research, Cambridge, MA, 02139, USA

    Kathrin Plath

  4. Genentech Hall, Room S372B, 600 16th Street, San Francisco, CA, 94143-2200, USA

    Barbara Panning

Authors
  1. Cecile C. de la Cruz
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  2. Jia Fang
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  3. Kathrin Plath
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  4. Kathleen A. Worringer
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  5. Dmitri A. Nusinow
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  6. Yi Zhang
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  7. Barbara Panning
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Correspondence to Barbara Panning.

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Communicated by R. Paro

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Fig8

Levels of Suz12 remain constant throughout stem cell differentiation. a, b Immunostaining for Ezh2 (first column) and Eed (secong column) in (a) undifferentiated ES cells and (b) a transformed mouse fibroblast cell line. DAPI delianates the nucleus (third column) and the merge (fourth column) is an overlay of Ezh2 (green) and Eed (red). c, d Immunostaining for Suz12 (first column) and Eed (second column) in (c undifferentiated ES cells and (d a transformed mouse fibroblasts cell line. DAPI delineates the nucleus (third column) and the merge (fourth column) is an overlay of Suz12 (green) and Eed (red)

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de la Cruz, C.C., Fang, J., Plath, K. et al. Developmental regulation of Suz12 localization. Chromosoma 114, 183–192 (2005). https://doi.org/10.1007/s00412-005-0008-6

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