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Chromosoma

, Volume 114, Issue 3, pp 183–192 | Cite as

Developmental regulation of Suz12 localization

  • Cecile C. de la Cruz
  • Jia Fang
  • Kathrin Plath
  • Kathleen A. Worringer
  • Dmitri A. Nusinow
  • Yi Zhang
  • Barbara Panning
Research Article

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.

Keywords

Embryonic Stem Cell IMR90 Cell Embryonic Stem Cell Differentiation Position Effect Variegation Trophoblast Stem 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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.

Supplementary material

412_2005_8_Fig8_ESM.gif (103 kb)

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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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Cecile C. de la Cruz
    • 1
  • Jia Fang
    • 2
  • Kathrin Plath
    • 3
  • Kathleen A. Worringer
    • 1
  • Dmitri A. Nusinow
    • 1
  • Yi Zhang
    • 2
  • Barbara Panning
    • 1
    • 4
  1. 1.Department of Biochemistry and BiophysicsUniversity of CaliforniaSan FranciscoUSA
  2. 2.Department of Biochemistry and BiophysicsThe University of North CarolinaChapel HillUSA
  3. 3.Whitehead Institute for Biomedical ResearchCambridgeUSA
  4. 4.San FranciscoUSA

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