Epigenetic Regulation of Open Chromatin in Pluripotent Stem Cells

Kobayashi, Hiroshi; Lowe, Michael; Kikyo, Nobuaki

doi:10.1016/b978-0-12-800802-7.00001-0

Cited by 5 publications

(7 citation statements)

References 101 publications

(84 reference statements)

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“…In this work we provide insights into callus features, having specific gene expression patterns that sustain high proliferation rate, independently from maintaining the potential to initiate all lineages of the mature organism. It is generally accepted that mammalian embryonic stem (ES) cells maintain pluripotency through retaining globally open chromatin state by basal transcription, to confer transcriptional competence for developmental programs (54, 55). We identify related strategy in callus, of keeping lineage-affiliated genes transcriptionally active, enabling the rapid response to signals, without the needs to go through the complex process of transcription.…”

Section: Discussionmentioning

confidence: 99%

The H3K27me3 epigenetic mark is crucial for callus cell identity and for the acquisition of new fate during root and shoot regeneration

Mandel

Landau

Kaplan

et al. 2022

Preprint

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We combined molecular, genomic and genetic approaches to study the molecular mechanisms underlying cell totipotency and competency to regenerate in Arabidopsis.By performing comparative analysis of mRNA-seq and chromatin landscapes between leaf differentiated cells and callus totipotent cells and between WT callus and calli derived from the emf2 mutant, exhibiting impaired regenerative capacity we revealed the following:1. That callus cells express numerous genes of many developmental pathways such as root, leaf, embryo, shoot, meristem and seed. This suggests a mechanism to allow rapid response to a signal by maintaining genes of all potential developmental pathways active, without the needs to release transcriptional silencing and to go through the intricate multistep process of transcription. 2. That key transcription factors that are sufficient to derive differentiation or organogenesis are silenced and marked by the H3K27me3. 3. That callus derived from the emf2 mutant which is impaired in setting the H3K27methylation, lost the capacity to regenerate and that 78 transcription factors from which 18 regulate flower development, where up-regulated compared with WT callus.Altogether our results suggest that competency to regenerate is achieved by keeping the chromatin of developmental genes active, and that upon a signal for cell fate switch, a mechanism to repress those genes is required to allow the one desired developmental pathway to dominate. When this mechanism is impaired the capacity to regenerate is decline.

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Section: Discussionmentioning

confidence: 99%

The H3K27me3 epigenetic mark is crucial for callus cell identity and for the acquisition of new fate during root and shoot regeneration

Mandel

Landau

Kaplan

et al. 2022

Preprint

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“…Thus far, the generally accepted mechanism is the LIF‐dependent activation of JAK2, which conveys its signals through STAT3 to the nucleus, leading to the expression of the core pluripotency gene network 58,59 . In addition, epigenetic regulation is an indispensable factor of pluripotency, by which undifferentiated/pluripotent ESC gene expressions are maintained in their open DNA/chromatin structures accessible for transcription activators 60,61 . Therefore, we postulated that the LIF‐JAK2‐STAT3 canonical pathway should be linked to the epigenetic regulation associated with the undifferentiated/pluripotent gene transcriptions.…”

Section: Discussionmentioning

confidence: 99%

“…58,59 In addition, epigenetic regulation is an indispensable factor of pluripotency, by which undifferentiated/pluripotent ESC gene expressions are maintained in their open DNA/chromatin structures accessible for transcription activators. 60,61 Therefore, we postulated that the LIF-JAK2-STAT3 canonical pathway should be linked to the epigenetic regulation associated with the undifferentiated/pluripotent gene transcriptions. In this study, we demonstrated that LIF treatment in mESC cultures establishes the active epigenetic signature associated with DNA/histone demethylation in the promoter regions of the core pluripotent genes, and that the LIFinduced epigenetic regulation is mediated by JAK2, but not by STAT3.…”

Section: Discussionmentioning

confidence: 99%

LIF maintains mouse embryonic stem cells pluripotency by modulating TET1 and JMJD2 activity in a JAK2-dependent manner

et al. 2021

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The LIF-JAK2-STAT3 pathway is the central signal transducer that maintains undifferentiated mouse embryonic stem cells (mESCs), which is achieved by the recruitment of activated STAT3 to the master pluripotency genes and activation of the gene transcriptions. It remains unclear, however, how the epigenetic status required for the master gene transcriptions is built into LIF-treated mESC cultures. In this study, Jak2, but not Stat3, in the LIF canonical pathway, establishes an open epigenetic status in the pluripotency gene promoter regions. Upon LIF activation, cytosolic JAK2 was translocalized into the nucleus of mESCs, and reduced DNA methylation (5mC levels) along with increasing DNA hydroxymethylation (5hmC) in the pluripotent gene (Nanog/Pou5f1) promoter regions. In addition, the repressive histone codes H3K9m3/H3K27m3 were reduced by JAK2. Activated JAK2 directly interacted with the core epigenetic enzymes TET1 and JMJD2, modulating its activity and promotes the DNA and histone demethylation, respectively. The JAK2 effects were attained by tyrosine phosphorylation on the epigenetic enzymes. The effects of JAK2 phosphorylation on the enzymes were diverse, but all were merged to the epigenetic signatures associated with open DNA/chromatin structures. Taken together, these results reveal a previously unrecognized epigenetic regulatory role of JAK2 as an important mediator of mESC maintenance.

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“…On the contrary, as cells commit to the different lineages, the condensed heterochromatin starts to predominate preventing the expression of genes characteristic of unrelated cell types [19]. Hence, the overall goal of the reprogramming process is to erase the epigenetic marks characteristic of the differentiated cells yielding a pristine status comparable to that of the pluripotent cell.…”

Section: Importance Of Epigenetic Mechanisms In Cellular Reprogrammingmentioning

confidence: 98%

Reprogramming cancer cells: A novel approach for cancer therapy or a tool for disease-modeling?

2015

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Epigenetic Regulation of Open Chromatin in Pluripotent Stem Cells

Cited by 5 publications

References 101 publications

The H3K27me3 epigenetic mark is crucial for callus cell identity and for the acquisition of new fate during root and shoot regeneration

The H3K27me3 epigenetic mark is crucial for callus cell identity and for the acquisition of new fate during root and shoot regeneration

LIF maintains mouse embryonic stem cells pluripotency by modulating TET1 and JMJD2 activity in a JAK2-dependent manner

Reprogramming cancer cells: A novel approach for cancer therapy or a tool for disease-modeling?

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