Rif1 promotes a repressive chromatin state to safeguard against endogenous retrovirus activation

Li, Pishun; Wang, Li; Bennett, Brian D.; Wang, Jiajia; Li, Jialun; Qin, Yufeng; Takaku, Motoki; Wade, Paul A.; Wong, Jiemin; Hu, Guang

doi:10.1093/nar/gkx884

Cited by 56 publications

(85 citation statements)

References 78 publications

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“…This model explains previous observations. The maintenance of higher order nuclear structures by RIF1 suggests how suppression of RIF1 perturbs transcription and heterochromatin formation (Dan, Liu et al, 2014, Li, Wang et al, 2017. It is also consistent with the finding that RIF1 associates with Lamin B1 (Foti et al, 2016).…”

Section: Discussionsupporting

confidence: 82%

The organizer of chromatin topology RIF1 ensures cellular resilience to DNA replication stress

Ribeyre

Lebdy

Patouillard

et al. 2019

Preprint

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Eukaryotic genomes are duplicated from thousands of replication origins that fire sequentially forming a defined spatiotemporal pattern of replication clusters. The importance of the organization of replisomes into functional clusters, also called replication factories, is still poorly understood. Here we identified the multifunctional protein RIF1 as a structural component of replication factories. RIF1 depletion did not impair the velocity of replication forks, neither in basic conditions nor in presence of a molecule that interferes with replication fork progression but increased the frequency of DNA lesions induced in S phase. Isolation of replication-associated proteins from RIF1-depleted cells revealed a major defect in the clustering of replication factors on nascent DNA, without any noticeable impact on DNA synthesis or replisome stability. We found that the changes in replication patterns commonly observed upon RIF1 depletion are induced by DNA replication stress. The data suggest that RIF1 encases replication factories to ensure the organization of replication clusters against chromatin rearrangements induced by DNA replication stress.

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Section: Discussionsupporting

confidence: 82%

The organizer of chromatin topology RIF1 ensures cellular resilience to DNA replication stress

Ribeyre

Lebdy

Patouillard

et al. 2019

Preprint

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“…Two-cell-like cells emerge from cells that express the transcription factor Zscan4 (Zscan4 + cells) [16], which are yet another subpopulation of ESC cultures constituting approximately 5% of the cell population [17,18]. Early-embryonic-like cells (Zscan4 + and 2-cell-like cells) can be induced in culture through the modulation of specific chromatin pathways, including the chromatin assembly factor 1 (CAF-1) [15] and the non-canonical polycomb repressive complex PRC1.6 [16,19], as well as the transcription factors Dux and Dppa2/4 [12,[20][21][22].…”

Section: Introductionmentioning

confidence: 99%

A distinct metabolic state arises during the emergence of 2‐cell‐like cells

et al. 2019

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Pluripotent stem cells are thought of as a surrogate of early developmental stages that sustain the capacity to generate all cell types in the body, thereby constituting an invaluable tool to address the mechanisms underlying cellular plasticity. In the mouse, cells resembling totipotent 2-cell-stage embryos (2-cell-like cells) arise at a very low frequency in embryonic stem cell (ESC) cultures. However, the extent to which these early-embryonic-like cells recapitulate the molecular features of the early embryo is unclear. Here, we have undertaken a characterization of some of the metabolic features of early-embryonic-like cells in culture. Our data indicate that early-embryonic-like cells exhibit decreased glycolytic and respiratory activity, lower levels of reactive oxygen species and increased glucose uptake, suggesting a shift of the metabolic programme during 2-cell-like cell reprogramming. Accordingly, we find that 2-cell-like cells can be induced by defined metabolites. Thus, in addition to their transcriptional and chromatin features, 2-cell-like cells recapitulate some of the metabolic features of their in vivo counterpart. Altogether, our work underscores a distinct metabolic state of early-embryonic-like cells and identifies compounds that can induce their emergence in vitro.

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“…In this pathway, 18 nt tRFs selectively antagonize RT action (an obligate step in replication for this TE class) while 22nt tRFs act as endo-siRNAs, participating in RISC-dependent destruction of TE transcripts. Additional pathways involving the proteins MARF1 (Su et al 2012), Stella (Huang et al 2017), RIF-1 (Li et al 2017) and TRIM28 (Tao et al 2018) are also important in TE repression and act through epigenetic and transcriptional modulation, but lie beyond the scope of this review. The most widely studied pathway involved in the control of TE expression is the PIWI/piRNA pathway.…”

Section: Control Of Te Expression During Reprogrammingmentioning

confidence: 96%

Transposons and the PIWI Pathway – Genome Defence in Gametes and Embryos

Russell

LaMarre

2018

Reproduction

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Hiding in plain sight within the genome of virtually every eukaryotic organism are large numbers of sequences known as transposable elements (TEs). These sequences often comprise 50% or more of the DNA in many mammals and are transcriptionally constrained by DNA methylation and repressive chromatin marks. Individual TEs, when relieved of these epigenetic constraints, can readily move from one genomic location to another, either directly or through RNA intermediates. Demethylation and removal of repressive histone marks during epigenetic reprogramming stages of gametogenesis and embryogenesis render the genome particularly susceptible to increased TE mobilization, which has significant implications for the fidelity of genome replication and subsequent viability of the progeny. Importantly however, TEs have functionally integrated themselves into developmental events to the extent that complete suppression precludes normal gamete and embryo development. Consequently, multiple mechanisms have evolved to limit the extent of TE expression and mobilization during reprogramming without completely suppressing it. One of the most important TE repression mechanisms is the PIWI/piRNA pathway, in which 25 - 32 nucleotide RNA molecules known as piRNAs associate with Argonaute proteins from the PIWI clade to form piRISC complexes. These complexes target and silence TEs post-transcriptionally and through the induction of epigenetic changes at the loci from which they are expressed. This review will briefly discuss the intricate molecular détente between TE expression and its suppression by the PIWI pathway, with particular emphasis on mammalian species including human, bovine and murine.

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Rif1 promotes a repressive chromatin state to safeguard against endogenous retrovirus activation

Cited by 56 publications

References 78 publications

The organizer of chromatin topology RIF1 ensures cellular resilience to DNA replication stress

The organizer of chromatin topology RIF1 ensures cellular resilience to DNA replication stress

A distinct metabolic state arises during the emergence of 2‐cell‐like cells

Transposons and the PIWI Pathway – Genome Defence in Gametes and Embryos

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