Epigenetic Priming of Enhancers Predicts Developmental Competence of hESC-Derived Endodermal Lineage Intermediates

Wang, Allen; Yue, Feng; Li, Yan; Xie, Ruiyu; Harper, Thomas K.; Patel, Nisha; Muth, Kayla; Palmer, Jeffrey D.; Qiu, Yunjiang; Wang, Jinzhao; Lam, Dieter K.; Raum, Jeffrey C.; Stoffers, Doris A.; Ren, Bing; Sander, Maike

doi:10.1016/j.stem.2015.02.013

Cited by 221 publications

(291 citation statements)

References 52 publications

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“…In mammalian systems, a fraction of enhancers have been shown to be poised prior to activation (Creyghton et al 2010;Rada-Iglesias et al 2011;Wamstad et al 2012;Wang et al 2015). This may be because the primed state already resembles the poised state or because enhancer activation occurs in a more sequential fashion by multiple patterning signals.…”

Section: Discussionmentioning

confidence: 99%

“…Only a small fraction of poised enhancers are usually activated during lineage development (Rada-Iglesias et al 2011;Bonn et al 2012;Wamstad et al 2012). Instead, many enhancers that are poised in a cell type are active in related cell types (Bonn et al 2012;Junion et al 2012;Wang et al 2015). This not only questions the strict temporal model in which the poised enhancer state precedes enhancer activation but also suggests a role for poised enhancers in tissue patterning.…”

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confidence: 99%

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Drosophilapoised enhancers are generated during tissue patterning with the help of repression

Koenecke

Johnston

et al. 2016

Preprint

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Histone modifications are frequently used as markers for enhancer states, but how to interpret enhancer states in the context of embryonic development is not clear. The poised enhancer signature, involving H3K4me1 and low levels of H3K27ac, has been reported to mark inactive enhancers that are poised for future activation. However, future activation is not always observed, and alternative reasons for the widespread occurrence of this enhancer signature have not been investigated. By analyzing enhancers during dorsal-ventral (DV) axis formation in the Drosophila embryo, we find that the poised enhancer signature is specifically generated during patterning in the tissue where the enhancers are not induced, including at enhancers that are known to be repressed by a transcriptional repressor. These results suggest that, rather than serving exclusively as an intermediate step before future activation, the poised enhancer state may be a mark for spatial regulation during tissue patterning. We discuss the possibility that the poised enhancer state is more generally the result of repression by transcriptional repressors.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Drosophilapoised enhancers are generated during tissue patterning with the help of repression

Koenecke

Johnston

et al. 2016

Preprint

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“…However, the extinction of corticotropespecific enhancers was at best partial in this model. Nonetheless, these observations indicate that Pax7 has the ability to not only activate a subset of enhancers but also to repress others, a property that is shared with other pioneer factors (Watts et al 2011;Wang et al 2015).…”

Section: Pax7 Opens a New Enhancer Repertoirementioning

confidence: 95%

Epigenetic Mechanisms of Pituitary Cell Fate Specification

Drouin

2016

Stem Cells in Neuroendocrinology

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Pituitary progenitor or stem cells present in the pituitary primordium during development are the source of hormone-producing cells of the adult pituitary. These stem cells are maintained in the adult tissue and they can be recruited to maintain or replenish differentiated pituitary cells. We currently have only limited insight into the mechanisms that trigger progenitor engagement into one or the other pituitary differentiation pathway. While transcription factors that drive terminal differentiation have been identified for different lineages, current evidence suggests that initial engagement of progenitors into differentiation may be due to earlier-acting factors. One such factor expressed at the transition between progenitor and differentiated state was identified in the intermediate lobe; this factor, Pax7, exerts its action through a pioneer factor activity. Pioneer transcription factors have the unique ability to bind target sequences in compacted chromatin and to initiate chromatin "opening" for recruitment of other transcription factors. Pax7 accomplishes this process on about 2500 enhancers genome-wide, allowing for Tpit recruitment at a subset for implementation of the melanotrope-specific program of gene expression. Current knowledge about this process is reviewed here, together with a discussion of future challenges in order to understand the unique properties of pioneer transcription factor action and cell reprogramming through chromatin remodelling.

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“…Moreover, the acquisition of a poising state – i.e. H3K4 nucleosome monomethylation – at enhancers in specific genes is essential for the ability of endodermal intermediates to respond to inductive signals during pancreatic and hepatic differentiation of human ESCs 43. In order to obtain a deeper understanding of the mechanisms regulating heterogeneity in PSCs, different studies have been performed based on the imposition of different growth conditions – e.g.…”

Section: Pluripotent State Gene Expression Heterogeneity Is Tightly Rmentioning

confidence: 99%

Modeling heterogeneity in the pluripotent state: A promising strategy for improving the efficiency and fidelity of stem cell differentiation

Angarica

Sol

2016

BioEssays

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Pluripotency can be considered a functional characteristic of pluripotent stem cells (PSCs) populations and their niches, rather than a property of individual cells. In this view, individual cells within the population independently adopt a variety of different expression states, maintained by different signaling, transcriptional, and epigenetics regulatory networks. In this review, we propose that generation of integrative network models from single cell data will be essential for getting a better understanding of the regulation of self‐renewal and differentiation. In particular, we suggest that the identification of network stability determinants in these integrative models will provide important insights into the mechanisms mediating the transduction of signals from the niche, and how these signals can trigger differentiation. In this regard, the differential use of these stability determinants in subpopulation‐specific regulatory networks would mediate differentiation into different cell fates. We suggest that this approach could offer a promising avenue for the development of novel strategies for increasing the efficiency and fidelity of differentiation, which could have a strong impact on regenerative medicine.

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Epigenetic Priming of Enhancers Predicts Developmental Competence of hESC-Derived Endodermal Lineage Intermediates

Cited by 221 publications

References 52 publications

Drosophilapoised enhancers are generated during tissue patterning with the help of repression

Drosophilapoised enhancers are generated during tissue patterning with the help of repression

Epigenetic Mechanisms of Pituitary Cell Fate Specification

Modeling heterogeneity in the pluripotent state: A promising strategy for improving the efficiency and fidelity of stem cell differentiation

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