457zygotic genome activation (Table 9.1) (Wormington and Brown 1983 ; De La Fuente
and Eppig 2001 ; Bachvarova and Davidson 1966 ; Woodland and Gurdon 1969 ;
Newport and Kirschner 1982a). In Xenopus, large-scale zygotic transcription is not
activated until the 12th embryonic cleavage, approximately 6–7 h after fertilization
(Newport and Kirschner 1982a). In zebrafish, large-scale zygotic gene activation is
not observed until the tenth cleavage division (Kane and Kimmel 1993 ). In medaka,
large-scale zygotic transcription was reported to begin around division 11–12
(Aizawa et al. 2003 ). The major wave of zygotic transcription in mammals is
delayed from one to several days, depending on the species, and occurs after fewer
cell divisions than observed in nonmammalian vertebrates. In mice and rabbits, the
major wave of zygotic gene activation is established by the 2-cell stage, whereas in
cows, sheep, pigs, and humans, major zygotic transcription begins at the 4- to
16-cell stage (Telford et al. 1990 ; Li et al. 2013 ; Hamatani et al. 2004 ; Wang et al.
2004 ; Zeng and Schultz 2005 ; Flach et al. 1982 ; Tesarik et al. 1988 ; Sawicki et al.
1981 ; Park et al. 2013 ; Xue et al. 2013 ; Aoki et al. 1997 ).
While the time until zygotic gene activation varies between organisms, it is
highly reproducible in a given species (Table 9.1). Furthermore, most species that
delay large-scale ZGA nevertheless demonstrate an earlier, minor wave of zygotic
transcription (reviewed by Tadros and Lipshitz 2009 ; Baroux et al. 2008 ; Lee et al.
2014 ), consistent with mechanisms that both suppress early transcription and acti-
vate zygotic genes at the appropriate stage. The following sections review the evi-
dence that early embryos have the capacity for transcription despite global repression
of most zygotic genes and discuss the regulation of zygotic gene activation, includ-
ing potential mechanisms to regulate the timing of zygotic gene activation.
9.3.2 Transcriptional Repression in Pre-MBT Embryos
Despite the limited zygotic transcription after fertilization in vertebrates, the basal
transcriptional machinery is present in oocytes and early embryos of Xenopus and
other amphibians, zebrafish, mouse, and other mammals (Brown 2004 ; Veenstra
2002 ; Wiekowski et al. 1993 ; Li et al. 2013 ; Lee et al. 2014 ), as are multiple gene
specific transcription factors. These findings suggest that the low level of transcrip-
tion is due to a repressive mechanism that functions until the MBT/ZGA, as dis-
cussed further in Sect. 9.3.5.
For example, RNA polymerases (RNAP) I, II, and III are present in Xenopus
oocytes and eggs, which have served as an abundant source for purification of poly-
merases and preparation of extracts competent for transcription of exogenous tem-
plates (Roeder 1974a, b). Importantly, RNAPII is present in an active form in early
embryos. RNAPII is phosphorylated in a repeat sequence within the C-terminal
domain in manner that correlates with its initiating (serine-5 phosphorylated) and
elongating (serine-2 phosphorylated) state. In vivo, RNAPII phosphorylated at serine-
2 is detectable in cleavage-stage embryos, consistent with a low level of transcription
before the MBT. Although several studies reported that serine-2 phosphorylation
9 Cell Cycle Remodeling and Zygotic Gene Activation at the Midblastula Transition