Mitotic binding of Esrrb marks key regulatory regions of the pluripotency network

Festuccia, Nicola; Dubois, Agnès; Vandormael-Pournin, Sandrine; Tejeda, Elena Gallego; Mouren, Adrien; Bessonnard, Sylvain; Mueller, Florian; Proux, Caroline; Cohen-Tannoudji, Michel; Navarro, Pablo

doi:10.1038/ncb3418

Cited by 141 publications

(246 citation statements)

References 61 publications

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“…The recent report that ESRRB acts as a mitotic bookmark of key regulatory elements during ESC cell division (Festuccia et al , 2016) is relevant to the above model. As mitosis is accompanied by eviction of several TFs from the chromatin, bookmarking by ESRRB may allow the rapid reassembly of the pluripotency network in early G1 (Festuccia et al , 2016).…”

Section: Discussionmentioning

confidence: 95%

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Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation

et al. 2018

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Self‐renewal of embryonic stem cells (ESCs) cultured in LIF/fetal calf serum (FCS) is incomplete with some cells initiating differentiation. While this is reflected in heterogeneous expression of naive pluripotency transcription factors (TFs), the link between TF heterogeneity and differentiation is not fully understood. Here, we purify ESCs with distinct TF expression levels from LIF/FCS cultures to uncover early events during commitment from naïve pluripotency. ESCs carrying fluorescent Nanog and Esrrb reporters show Esrrb downregulation only in Nanoglow cells. Independent Esrrb reporter lines demonstrate that Esrrbnegative ESCs cannot effectively self‐renew. Upon Esrrb loss, pre‐implantation pluripotency gene expression collapses. ChIP‐Seq identifies different regulatory element classes that bind both OCT4 and NANOG in Esrrbpositive cells. Class I elements lose NANOG and OCT4 binding in Esrrbnegative ESCs and associate with genes expressed preferentially in naïve ESCs. In contrast, Class II elements retain OCT4 but not NANOG binding in ESRRB‐negative cells and associate with more broadly expressed genes. Therefore, mechanistic differences in TF function act cumulatively to restrict potency during exit from naïve pluripotency.

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Section: Discussionmentioning

confidence: 95%

“…As mitosis is accompanied by eviction of several TFs from the chromatin, bookmarking by ESRRB may allow the rapid reassembly of the pluripotency network in early G1 (Festuccia et al , 2016). Declining ESRRB levels may therefore impair the reactivation of key pluripotency enhancers after mitosis.…”

Section: Discussionmentioning

confidence: 99%

Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation

et al. 2018

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“…3). In addition to chromatin modifiers, a select group of transcription factors such as FOXA1, GATA1, RUNX2, ESRRB and RBPJ also bind and 'bookmark' mitotic chromatin (Caravaca et al, 2013;Festuccia et al, 2016;Kadauke et al, 2012;Lake et al, 2014;Young et al, 2007). Interestingly, however, these factors maintain mitotic chromatin binding at only a subset of the specific sites bound during interphase (Caravaca et al, 2013;Kadauke et al, 2012).…”

Section: Box 1 Mitotic Bookmarkingmentioning

confidence: 99%

Cycling through developmental decisions: how cell cycle dynamics control pluripotency, differentiation and reprogramming

2016

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A strong connection exists between the cell cycle and mechanisms required for executing cell fate decisions in a wide-range of developmental contexts. Terminal differentiation is often associated with cell cycle exit, whereas cell fate switches are frequently linked to cell cycle transitions in dividing cells. These phenomena have been investigated in the context of reprogramming, differentiation and trans-differentiation but the underpinning molecular mechanisms remain unclear. Most progress to address the connection between cell fate and the cell cycle has been made in pluripotent stem cells, in which the transition through mitosis and G1 phase is crucial for establishing a window of opportunity for pluripotency exit and the initiation of differentiation. This Review will summarize recent developments in this area and place them in a broader context that has implications for a wide range of developmental scenarios.

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“…However, some transcription factors do not abide by this rule and remain bound to specific genes on mitotic chromosomes. These so-called mitotic bookmarking transcription factors are involved in physiological processes such as phenotypic maintenance (Zaidi et al 2010(Zaidi et al , 2014Kadauke and Blobel 2013;Festuccia et al 2016) and ribosome biogenesis (Chen et al 2002;Grob et al 2014;Lopez-Camacho et al 2014) as well as pathological events such as oncogenic transformation (Blobel et al 2009;Pockwinse et al 2011;Zaidi et al 2014). However, the contribution of mitotic chromosome retention to these functions remains unknown.…”

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confidence: 99%

A role for mitotic bookmarking of SOX2 in pluripotency and differentiation

et al. 2016

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Mitotic bookmarking transcription factors remain bound to chromosomes during mitosis and were proposed to regulate phenotypic maintenance of stem and progenitor cells at the mitosis-to-G1 (M-G1) transition. However, mitotic bookmarking remains largely unexplored in most stem cell types, and its functional relevance for cell fate decisions remains unclear. Here we screened for mitotic chromosome binding within the pluripotency network of embryonic stem (ES) cells and show that SOX2 and OCT4 remain bound to mitotic chromatin through their respective DNA-binding domains. Dynamic characterization using photobleaching-based methods and single-molecule imaging revealed quantitatively similar specific DNA interactions, but different nonspecific DNA interactions, of SOX2 and OCT4 with mitotic chromatin. Using ChIP-seq (chromatin immunoprecipitation [ChIP] combined with high-throughput sequencing) to assess the genome-wide distribution of SOX2 on mitotic chromatin, we demonstrate the bookmarking activity of SOX2 on a small set of genes. Finally, we investigated the function of SOX2 mitotic bookmarking in cell fate decisions and show that its absence at the M-G1 transition impairs pluripotency maintenance and abrogates its ability to induce neuroectodermal differentiation but does not affect reprogramming efficiency toward induced pluripotent stem cells. Our study demonstrates the mitotic bookmarking property of SOX2 and reveals its functional importance in pluripotency maintenance and ES cell differentiation.

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Mitotic binding of Esrrb marks key regulatory regions of the pluripotency network

Cited by 141 publications

References 61 publications

Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation

Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation

Cycling through developmental decisions: how cell cycle dynamics control pluripotency, differentiation and reprogramming

A role for mitotic bookmarking of SOX2 in pluripotency and differentiation

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