How cells build totipotency and pluripotency: nuclear, chromatin and transcriptional architecture

Dang‐Nguyen, Thanh Quang; Torres-Padilla, Maria-Elena

doi:10.1016/j.ceb.2015.04.006

Cited by 19 publications

(15 citation statements)

References 50 publications

(49 reference statements)

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“…In response to signaling and spatial cues, transcription factors engage with the epigenome to culminate in gene expression patterns that establish cell identity (Kelsey et al, 2017). The abundance of particular epigenetic modifications changes dynamically during development (Dang-Nguyen and Torres-Padilla, 2015;Smith and Meissner, 2013).…”

Section: Introductionmentioning

confidence: 99%

Dot1L methyltransferase activity is a barrier to acquisition of pluripotency but not transdifferentiation

Wille

Sridharan

2019

Preprint

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Pluripotent stem cells (PSCs) exist in a unique state poised to differentiate into any of the somatic cell types in part by maintaining an open chromatin structure. How these extraordinary cells suppress spurious transcription in the relative absence of repressive epigenetic modifications is poorly understood. PSCs are depleted for transcriptional elongation associated epigenetic modifications, primarily H3K79me2. Although H3K79me2 is found on thousands of genes, inhibiting the enzymatic activity of its methyltransferase, Dot1L results in few transcriptional changes, the majority of which are upregulated. During reprogramming of somatic cells to pluripotency, Dot1L inhibition (Dot1Li) at the midpoint is particularly effective at yielding greater number of colonies. Further, Dot1Li enhances reprogramming beyond early phases such as the mesenchymal to epithelial transition and from already epithelial cell types such as keratinocytes. Modulation of single genes from the DotLi transcriptional response cannot replace its function. Significantly, Dot1L inhibition does not enhance lineage conversion to neurons. Taken together, our results indicate that H3K79me is not a universal barrier of cell fate transitions but specifically protects cells from reverting to the pluripotent state.

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Section: Introductionmentioning

confidence: 99%

Dot1L methyltransferase activity is a barrier to acquisition of pluripotency but not transdifferentiation

Wille

Sridharan

2019

Preprint

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“…Most histones are stably associated with DNA, and new incorporation occurs mostly during DNA replication, although a smaller histone fraction, including, notably, histone variants, exhibits dynamic exchange with the soluble pool of nucleoplasmic histones ( 2 ). In ESCs this dynamic interaction is enhanced ( 3 , 4 ), resulting in a hyperdynamic chromatin state in ESCs, which is believed to be functionally important for the maintenance of pluripotency ( 3 , 5 – 9 ).…”

Section: Introductionmentioning

confidence: 99%

A hyperdynamic H3.3 nucleosome marks promoter regions in pluripotent embryonic stem cells

Schlesinger

Kaffe

Melcer

et al. 2017

Nucleic Acids Research

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Histone variants and their chaperones are key regulators of eukaryotic transcription, and are critical for normal development. The histone variant H3.3 has been shown to play important roles in pluripotency and differentiation, and although its genome-wide patterns have been investigated, little is known about the role of its dynamic turnover in transcriptional regulation. To elucidate the role of H3.3 dynamics in embryonic stem cell (ESC) biology, we generated mouse ESC lines carrying a single copy of a doxycycline (Dox)-inducible HA-tagged version of H3.3 and monitored the rate of H3.3 incorporation by ChIP-seq at varying time points following Dox induction, before and after RA-induced differentiation. Comparing H3.3 turnover profiles in ESCs and RA-treated cells, we identified a hyperdynamic H3.3-containing nucleosome at the −1 position in promoters of genes expressed in ESCs. This dynamic nucleosome is restricted and shifted downstream into the +1 position following differentiation. We suggest that histone turnover dynamics provides an additional mechanism involved in expression regulation, and that a hyperdynamic −1 nucleosome marks promoters in ESCs. Our data provide evidence for regional regulation of H3.3 turnover in ESC promoters, and calls for testing, in high resolution, the dynamic behavior of additional histone variants and other structural chromatin proteins.

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“…This transition correlates with changes in the compaction of chromatin within the nucleus [28,29]. A similar event likely occurs in most or all animal embryos [30][31][32][33][34][35].…”

Section: The Multipotency-to-commitment Transition (Mct)mentioning

confidence: 72%

The multipotency‐to‐commitment transition in Caenorhabditis elegans—implications for reprogramming from cells to organs

2018

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In animal embryos, cells transition from a multipotential state, with the capacity to adopt multiple fates, into an irreversible, committed state of differentiation. This multipotency-to-commitment transition (MCT) is evident from experiments in which cell fate is reprogrammed by transcription factors for cell type-specific differentiation, as has been observed extensively in Caenorhabditis elegans. Although factors that direct differentiation into each of the three germ layer types cannot generally reprogram cells after the MCT in this animal, transcription factors for endoderm development are able to do so in multiple differentiated cell types. In one case, these factors can redirect the development of an entire organ in the process of "transorganogenesis". Natural transdifferentiation also occurs in a small number of differentiated cells during normal C. elegans development. We review these reprogramming and transdifferentiation events, highlighting the cellular and developmental contexts in which they occur, and discuss common themes underlying direct cell lineage reprogramming. Although certain aspects may be unique to the model system, growing evidence suggests that some mechanisms are evolutionarily conserved and may shed light on cellular plasticity and disease in humans.

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How cells build totipotency and pluripotency: nuclear, chromatin and transcriptional architecture

Cited by 19 publications

References 50 publications

Dot1L methyltransferase activity is a barrier to acquisition of pluripotency but not transdifferentiation

Dot1L methyltransferase activity is a barrier to acquisition of pluripotency but not transdifferentiation

A hyperdynamic H3.3 nucleosome marks promoter regions in pluripotent embryonic stem cells

The multipotency‐to‐commitment transition in Caenorhabditis elegans—implications for reprogramming from cells to organs

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