S4O). We also observed H3K27ac spreading at the
Hox cluster (fig. S5A), which suggests that loss of
pre-ZGA H3K27me3 and accumulation of H3K27ac
resulted in altered chromatin states at this locus
and caused the transcriptional defects later in
development (fig. S3N). The accumulation of
H3K27ac at the Hox cluster in E(z)-TS embryos
was not reversed after shifting the embryos to
the permissive temperature at ZGA, consistent
with persistent homeotic transformation and
lethality (Fig. 3, C to E, and fig. S5A). Thus, maternally inherited and pre-ZGA H3K27me3 restricts
lineage-specific gene expression and regulatory
regions by preventing their precocious activation
Our results indicate that H3K27me3 is intergenerationally inherited from the maternal germ
line and resists reprogramming events during
early embryogenesis in Drosophila. At lower levels,
H3K27me3 is also retained in mature sperm,
which suggests that epigenetic information carried
by modified histones is also contributed to the
zygote paternally (2, 3, 8, 10, 19). Propagation of
germ line–inherited H3K27me3 by maternally
supplied PRC2 prevents the aberrant spread of
active histone marks and ectopic expression of
lineage regulators at ZGA. Our data suggest that
a Polycomb-based chromatin signature represses
and poises early developmental enhancers at
ZGA. PRC1 was shown to be required only after
ZGA (32). Therefore, although PRC1 has also been
shown to be retained through DNA replication
and potentially provide maintenance of transcriptional silencing through cell division (33), we suggest that the Polycomb intergenerational epigenetic
memory of repressed states is propagated solely
through the H3K27me3 mark. We also show that
the Hox cluster resides in a repressed chromatin
state, marked by H3K27me3, throughout early
embryogenesis until its chromatin is remodeled
in a segment-specific manner later in development
(23), as suggested for vertebrates (34). Therefore,
the epigenetic memory imposed by PRC2 is germ
line–inherited and appears to function much earlier
than previously appreciated (5). H3K27me3 was
recently shown to be present on pre-implantation
embryo chromatin in mouse; we speculate that
H3K27me3 could have similar functions during
mammalian embryogenesis (35). We further propose that environmentally induced alterations
of histone modifications in the adult germ line
could contribute to transgenerational epigenetic
REFERENCES AND NOTES
1. H. D. Morgan, F. Santos, K. Green, W. Dean, W. Reik, Hum. Mol.
Genet. 14 (suppl. 1), R47–R58 (2005).
2. E. A. Miska, A. C. Ferguson-Smith, Science 354, 59–63 (2016).
3. U. Sharma, O. J. Rando, Cell Metab. 25, 544–558 (2017).
4. J. A. Simon, R. E. Kingston, Nat. Rev. Mol. Cell Biol. 10,
5. U. Grossniklaus, R. Paro, Cold Spring Harb. Perspect. Biol.
6, a019331 (2014).
6. N. Iovino, F. Ciabrelli, G. Cavalli, Dev. Cell 26, 431–439 (2013).
7. W. Mu, J. Starmer, A. M. Fedoriw, D. Yee, T. Magnuson, Genes
Dev. 28, 2056–2069 (2014).
8. U. Brykczynska et al., Nat. Struct. Mol. Biol. 17, 679–687
9. S. Hontelez et al., Nat. Commun. 6, 10148 (2015).
10. S. S. Hammoud et al., Nature 460, 473–478 (2009).
11. X. Y. Li, M. M. Harrison, J. E. Villalta, T. Kaplan, M. B. Eisen,
eLife 3, 03737 (2014).
12. N. L. Vastenhouw et al., Nature 464, 922–926 (2010).
13. H. Zheng et al., Mol. Cell 63, 1066–1079 (2016).
14. L. J. Gaydos, W. Wang, S. Strome, Science 345, 1515–1518
15. M. Samson et al., PLOS Genet. 10, e1004588 (2014).
16. G. Struhl, D. Brower, Cell 31, 285–292 (1982).
17. R. S. Jones, W. M. Gelbart, Genetics 126, 185–199 (1990).
18. A. H. Elnfati, D. Iles, D. Miller, Genom. Data 7, 175–177 (2015).
19. S. F. Wu, H. Zhang, B. R. Cairns, Genome Res. 21, 578–589
20. T. Cheutin, G. Cavalli, PLOS Genet. 8, e1002465 (2012).
21. A. J. Haigh, W. A. MacDonald, V. K. Lloyd, Genetics 169,
22. W. Tadros, H. D. Lipshitz, Development 136, 3033–3042
23. S. K. Bowman et al., eLife 3, e02833 (2014).
24. M. D. Schroeder, C. Greer, U. Gaul, Development 138,
25. F. Pelegri, R. Lehmann, Genetics 136, 1341–1353 (1994).
26. Ö. Copur, J. Müller, Development 140, 3478–3485 (2013).
27. R. Margueron et al., Nature 461, 762–767 (2009).
28. H. M. Herz et al., Science 345, 1065–1070 (2014).
29. A. Rada-Iglesias et al., Nature 470, 279–283 (2011).
30. S. Bonn et al., Nat. Genet. 44, 148–156 (2012).
31. E. Z. Kvon et al., Nature 512, 91–95 (2014).
32. J. L. Haynie, Dev. Biol. 100, 399–411 (1983).
33. N. J. Francis, N. E. Follmer, M. D. Simon, G. Aghia, J. D. Butler,
Cell 137, 110–122 (2009).
34. N. Soshnikova, D. Duboule, Science 324, 1320–1323
35. X. Liu et al., Nature 537, 558–562 (2016).
We thank the Iovino lab, in particular D. Latreille, D. Ibarra-Morales, and
V. Asimi; our colleagues A. Akhtar, T. Jenuwein, P. Becker, R. Sawarkar,
E. Trompouki, and especially T. Boehm for critical reading of the
manuscript; the Bioinformatics and Sequencing facilities at the Max
Planck Institute of Immunobiology and Epigenetics (MPI-IE) (T. Manke,
U. Boenisch, L. Arrigoni, and in particular D. Ryan); C. Hug and
J. M. Vaquerizas (MPI for Molecular Biomedicine, Muenster, Germany)
for initial help in RNA-seq data analysis; S. De Renzis (EMBL) for
initial help in staging of the embryos; the Imaging facility, Proteomics
facility, and Fly facility at MPI-IE; L. Ringrose and V. Pirrotta for sharing
fly stocks; and J. Mueller [E(z)], T. Jenuwein (H3K27me3 and
H3K27me2), and the Developmental Studies Hybridoma Bank (Abd-B)
for antibodies. The Bloomington Drosophila Stock Center (NIH
P40OD018537) and the Transgenic RNAi Project at Harvard Medical
School (NIH/NIGMS R01-GM084947) provided fly stocks used in this
study. Supported by the Max Planck Society and IMPRS program
(F. Z. and E.L.); German Research Foundation (DFG) CRC992, Project
B06 and Z01 (R. S. and F. K.); Australian Research Council Discovery
Early Career Researcher Award DE140101962 (O.B.); and the Max
Planck Society and DFG CRC992, Project B06 (N.I.). All the data are
deposited at ENA ( www.ebi.ac.uk/ena) PRJEB18481 (primary
accession), ERP020413 (secondary accession).
Figs. S1 to S5
Tables S1 to S3
Databases S1 to S4
5 December 2016; accepted 16 June 2017
216 14 JULY 2017 • VOL 357 ISSUE 6347 sciencemag.org SCIENCE
RESEARCH | REPORTS