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.
MeSH Terms
Animals
Carrier Proteins/genetics,metabolism,physiology
Cell Differentiation
DNA-Binding Proteins/metabolism
Gene Expression Regulation, Developmental/genetics,physiology
Histone Methyltransferases
Histone-Lysine N-Methyltransferase/metabolism
Histones/metabolism
Humans
Methylation
Mice
Neoplasm Proteins
Nuclear Proteins
Polycomb Repressive Complex 2
Protein Methyltransferases
RNA, Long Noncoding
RNA, Small Interfering/genetics,metabolism
RNA, Untranslated/metabolism
Recombinant Fusion Proteins/metabolism
Repressor Proteins/metabolism
Stem Cells/metabolism
Transcription Factors/metabolism
Transfection
Trophoblasts/cytology,metabolism
X Chromosome Inactivation
Chemicals
Carrier Proteins
DNA-Binding Proteins
EED protein, human
Histones
Neoplasm Proteins
Nuclear Proteins
RNA, Long Noncoding
RNA, Small Interfering
RNA, Untranslated
Recombinant Fusion Proteins
Repressor Proteins
SUZ12 protein, human
Transcription Factors
XIST non-coding RNA
Histone Methyltransferases
Protein Methyltransferases
EZH1 protein, human
Histone-Lysine N-Methyltransferase
Polycomb Repressive Complex 2
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
de la Cruz Cecile C
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.
Fang Jia
Plath Kathrin
Worringer Kathleen A
Nusinow Dmitri A
Zhang Yi
Panning Barbara
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