Developmental regulation of Suz12 localization
- 319 Downloads
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.
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.
- Kuzmichev A, Margueron R, Vaquero A, Preissner TS, Scher M, Kirmizis A, Ouyang X, Brockdorff N, Abate-Shen C, Farnham P, Reinberg D (2005) Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation. Proc Natl Acad Sci U S A 102:1859–1864CrossRefPubMedGoogle Scholar
- Silva J, Mak W, Zvetkova I, Appanah R, Nesterova TB, Webster Z, Peters AH, Jenuwein T, Otte AP, Brockdorff N (2003) Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed–Enx1 polycomb group complexes. Dev Cell 4:481–495CrossRefPubMedGoogle Scholar