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Chromatin signature of embryonic pluripotency is established during genome activation


After fertilization the embryonic genome is inactive until transcription is initiated during the maternal–zygotic transition1,2,3. This transition coincides with the formation of pluripotent cells, which in mammals can be used to generate embryonic stem cells. To study the changes in chromatin structure that accompany pluripotency and genome activation, we mapped the genomic locations of histone H3 molecules bearing lysine trimethylation modifications before and after the maternal–zygotic transition in zebrafish. Histone H3 lysine 27 trimethylation (H3K27me3), which is repressive, and H3K4me3, which is activating, were not detected before the transition. After genome activation, more than 80% of genes were marked by H3K4me3, including many inactive developmental regulatory genes that were also marked by H3K27me3. Sequential chromatin immunoprecipitation demonstrated that the same promoter regions had both trimethylation marks. Such bivalent chromatin domains also exist in embryonic stem cells and are thought to poise genes for activation while keeping them repressed4,5,6,7,8. Furthermore, we found many inactive genes that were uniquely marked by H3K4me3. Despite this activating modification, these monovalent genes were neither expressed nor stably bound by RNA polymerase II. Inspection of published data sets revealed similar monovalent domains in embryonic stem cells. Moreover, H3K4me3 marks could form in the absence of both sequence-specific transcriptional activators and stable association of RNA polymerase II, as indicated by the analysis of an inducible transgene. These results indicate that bivalent and monovalent domains might poise embryonic genes for activation and that the chromatin profile associated with pluripotency is established during the maternal–zygotic transition.

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Figure 1: Large-scale changes in chromatin modifications during maternal–zygotic transition.
Figure 2: Bivalent chromatin domains in zebrafish embryos.
Figure 3: Many inactive genes are monovalently marked with H3K4me3.
Figure 4: H3K4me3 occupancy in the absence of a sequence-specific transcriptional activator.

Accession codes

Primary accessions

Gene Expression Omnibus

Data deposits

ChIP–chip data is available under GEO accession number GSE20023; custom designed array platform is under accession number GPL9970.


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We thank members of the Schier laboratory for help and advice; H. G. Shin, L. Taing and Z. J. Wu for computational analysis and discussions; N. Follmer and B. Lilley for technical advice; and J. Dubrulle, N. Francis, R. Losick, S. Mango, T. van Opijnen and W. Talbot for discussions and critical reading of the manuscript. This work was supported by NIH grants to X.S.L. (1R01 HG004069) and A.F.S. (5R01 GM56211), and by EMBO and HFSP (LT-00090/2007) fellowships to N.L.V.

Author Contributions N.L.V. and A.F.S. designed the study. N.L.V. performed the experiments. Y.Z. performed computational analysis. N.L.V., Y.Z., J.R., X.S.L. and A.F.S. designed and performed data analysis. I.G.W. provided technical support. F.I. provided RNA profiling data. A.R. provided analytical advice. N.L.V. and A.F.S. interpreted the data and wrote the paper with support from co-authors.

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Correspondence to X. Shirley Liu or Alexander F. Schier.

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Supplementary Information

This file contains Supplementary Discussions 1-5, Supplementary Figures S1-S9 with legends and Supplementary References. (PDF 1626 kb)

Supplementary Table 1

This file contains Supplementary Table 1, which includes the list of analyzed genes and their status for H3K4me3, H3K27me3, H3K36me3 and RNA polymerase II in zebrafish blastomeres. (XLS 110 kb)

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Vastenhouw, N., Zhang, Y., Woods, I. et al. Chromatin signature of embryonic pluripotency is established during genome activation. Nature 464, 922–926 (2010).

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