Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage

Srinivasan, Rajini; Nady, Nataliya; Arora, Neiha; Hsieh, Laura J; Swigut, Tomek; Narlikar, Geeta J.; Wossidlo, Mark; Wysocka, Joanna

doi:10.1126/sciadv.aaz9115

Cited by 49 publications

(41 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ZSCAN4 depletion results in developmental arrest at the time of EGA in mice 28 and cattle 29 , supporting an important role for this TF. A recent report indicates that ZSCAN4 binds microsatellites in mouse embryos 49 . These binding sites would be problematic to identify in our analysis, given the difficulty of aligning short reads to repetitive sequences.…”

Section: Resultsmentioning

confidence: 99%

Chromatin remodeling in bovine embryos indicates species-specific regulation of genome activation

Halstead

Zhou

et al. 2020

Nat Commun

View full text Add to dashboard Cite

The shift from maternal to embryonic control is a critical developmental milestone in preimplantation development. Widespread transcriptomic and epigenetic remodeling facilitate this transition from terminally differentiated gametes to totipotent blastomeres, but the identity of transcription factors (TF) and genomic elements regulating embryonic genome activation (EGA) are poorly defined. The timing of EGA is species-specific, e.g., the timing of murine and human EGA differ significantly. To deepen our understanding of mammalian EGA, here we profile changes in open chromatin during bovine preimplantation development. Before EGA, open chromatin is enriched for maternal TF binding, similar to that observed in humans and mice. During EGA, homeobox factor binding becomes more prevalent and requires embryonic transcription. A cross-species comparison of open chromatin during preimplantation development reveals strong similarity in the regulatory circuitry underlying bovine and human EGA compared to mouse. Moreover, TFs associated with murine EGA are not enriched in cattle or humans, indicating that cattle may be a more informative model for human preimplantation development than mice.

show abstract

Section: Resultsmentioning

confidence: 99%

Chromatin remodeling in bovine embryos indicates species-specific regulation of genome activation

Halstead

Zhou

et al. 2020

Nat Commun

View full text Add to dashboard Cite

show abstract

“…The known role of ZSCAN4 in the re-activation of early embryonic genes and promotion of MERVL expression 37,38 , suggest that might be essential for successful 2C-like conversion. Moreover, ZSCAN4 has also been implicated in the maintenance of telomeres and genome stability of ESCs as well as in protecting the 2C embryo from DNA damage [41][42][43] . Thus, ZSCAN4 could participate in limiting the damage associated with the 2C-like conversion.…”

Section: Discussionmentioning

confidence: 99%

CTCF is a barrier for 2C-like reprogramming

et al. 2021

View full text Add to dashboard Cite

Totipotent cells have the ability to generate embryonic and extra-embryonic tissues. Interestingly, a rare population of cells with totipotent-like potential, known as 2 cell (2C)-like cells, has been identified within ESC cultures. They arise from ESC and display similar features to those found in the 2C embryo. However, the molecular determinants of 2C-like conversion have not been completely elucidated. Here, we show that the CCCTC-binding factor (CTCF) is a barrier for 2C-like reprogramming. Indeed, forced conversion to a 2C-like state by the transcription factor DUX is associated with DNA damage at a subset of CTCF binding sites. Depletion of CTCF in ESC efficiently promotes spontaneous and asynchronous conversion to a 2C-like state and is reversible upon restoration of CTCF levels. This phenotypic reprogramming is specific to pluripotent cells as neural progenitor cells do not show 2C-like conversion upon CTCF-depletion. Furthermore, we show that transcriptional activation of the ZSCAN4 cluster is necessary for successful 2C-like reprogramming. In summary, we reveal an unexpected relationship between CTCF and 2C-like reprogramming.

show abstract

“…Human NSD2-mediated PTEN methylation regulates cell responses to DNA damage [ 30 ]. It is recently discovered that DNA damage is induced by the depletion of MERVL activator Zscan4 [ 3 , 31 ]. Responses of ATR and CHK1 to replication stresses activate Zscan4 and MERVL [ 20 ], implying that DNA damage-induced replication stress and Zscan4 reciprocally regulate each other.…”

Section: Discussionmentioning

confidence: 99%

Nsd2 Represses Endogenous Retrovirus MERVL in Embryonic Stem Cells

Gao

Chen

Zhang

et al. 2021

Stem Cells International

View full text Add to dashboard Cite

The facilitates chromatin transcription (FACT) complex is a histone H2A/H2B chaperone, which represses endogenous retroviruses (ERVs) and transcription of ERV-chimeric transcripts. It binds to both transcription start site and gene body region. Here, we investigated the downstream targets of FACT complex to identify the potential regulators of MERVL, which is a key 2-cell marker gene. H3K36me2 profile was positively correlated with that of FACT component Ssrp1. Among H3K36me2 deposition enzymes, Nsd2 was downregulated after the loss of Ssrp1. Furthermore, we demonstrated that Nsd2 repressed the expression of ERVs without affecting the expression of pluripotency genes. The expression of MERVL and 2-cell genes was partially rescued by Nsd2 overexpression. The enrichment of H3K36me2 decreased on MERVL-chimeric gene in ESCs without Ssrp1. Our study discovers that Nsd2 is a repressor of MERVL, and FACT partially represses MERVL expression by regulating the expression of Nsd2 and its downstream H3K36me2.

show abstract

Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage

Cited by 49 publications

References 42 publications

Chromatin remodeling in bovine embryos indicates species-specific regulation of genome activation

Chromatin remodeling in bovine embryos indicates species-specific regulation of genome activation

CTCF is a barrier for 2C-like reprogramming

Nsd2 Represses Endogenous Retrovirus MERVL in Embryonic Stem Cells

Contact Info

Product

Resources

About