Nuclear reprogramming: the zygotic transcription program is established through an “erase-and-rebuild” strategy

Abstract

npgOocytes display a maternal-specific gene expression profile, which is switched to a zygotic profile when a haploid set of chromatin is passed on to the fertilized egg that develops into an embryo. The mechanism underlying this transcription reprogramming is currently unknown. Here we demonstrate that by the time when transcription is shut down in germinal vesicle oocytes, a range of general transcription factors and transcriptional regulators are dissociated from the chromatin. The global dissociation of chromatin factors (CFs) disrupts physical contacts between the chromatin and CFs and leads to erasure of the maternal transcription program at the functional level. Critical transcription factors and regulators remain separated from chromatin for a prolonged period, and become re-associated with chromatin shortly after pronuclear formation. This is followed temporally by the re-establishment of nuclear functions such as DNA replication and transcription. We propose that the maternal transcription program is erased during oogenesis to generate a relatively naïve chromatin and the zygotic transcription program is rebuilt de novo after fertilization. This process is termed as the "erase-and-rebuild" process, which is used to reset the transcription program, and most likely other nuclear processes as well, from a maternal one to that of the embryo. We further show in the accompanying paper (Gao T, et al., Cell Res 2007; 17:135-150.) that the same strategy is also employed to reprogram transcriptional profiles in somatic cell nuclear transfer and parthenogenesis, suggesting that this model is universally applicable to all forms of transcriptional reprogramming during early embryogenesis. Displacement of CFs from chromatin also offers an explanation for the phenomenon of transcription silence during the maternal to zygotic transition.

Nuclear reprogramming: the strategy used in normal development is also used in somatic cell nuclear transfer and parthenogenesis

“…As demonstrated in the accompanying paper [41] that an "erase-and-rebuild" strategy is used in normal development to reset the maternal transcriptional profile to that of the embryo, we show in this paper that during SCNT and parthenogenesis, CFs critical for transcription activation and regulation are dissociated from somatic nuclei and duplicated maternal chromatin, respectively, in manners analogous to the erasure process in oogenesis. Most CFs later become re-associated with pronuclei/chromatin during SCNT and parthenogenesis in a spatiotemporal manner similar to that in fertilized embryos.…”

“…Re-association between PPNs and CFs occurred in a manner similar to that in fertilized embryos [32][33][34]41].…”

“…We examined whether the "erase-and-rebuild" strategy used to reprogram gene expression profile in normal development [41] is also used in somatic cell nuclear transfer (SCNT) and parthenogenesis. It was found in this study that mature eggs retain the ability to dissociate chromatin factor (CFs) from chromatin/nuclei.…”

Erasure of the paternal transcription program during spermiogenesis: The first step in the reprogramming of sperm chromatin for zygotic development

“…5, Table 2, and data not shown). Once associated, the signals of SRG3, HDAC2, HP1␣, and TOPOII␣ persisted on the paternal chromatin throughout anaphase, PN1, and PN2, and their nuclear concentrations significantly increased in PN3 In contrast, most sperm nuclei were positive for TFIIB and Pol II before or during anaphase, negative by the PN1 stage, and became positive again in the male pronuclei by the PN3 stage (Table 2, data not shown, and Sun et al, 2007). TOPOII␤ was present in a small proportion of sperm nuclei before PN2 and in all pronuclei thereafter.…”

“…5, Table 2, and Sun et al, 2007). Several CFs, including TFIIB, SRG3, and HDAC2, appeared earlier and/or stronger in the male than in the female pronuclei.…”