Dynamics of RNA Polymerase II Pausing and Bivalent Histone H3 Methylation during Neuronal Differentiation in Brain Development

Liu, Jiancheng; Wu, Xiwei; Zhang, Heying; Pfeifer, Gerd P.; Lü, Qiang

doi:10.1016/j.celrep.2017.07.046

Cited by 49 publications

(44 citation statements)

References 48 publications

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“…A recent study by Liu J et al [ 54 ] looked at the developmental changes of the bivalent chromatin marks and paused Pol II during neuronal differentiation in the mouse brain, and noted in agreement to our study that genes involved in cell cycle and other catabolic processes show very high RNA pol II pausing. Unlike our study, Liu J et al [ 54 ] noted that bivalent marks primed neuronal specification genes for activation during differentiation. One of the possible reasons for the discrepancy might be that the data collected for eight cell types from public domain in this study does not have a well-defined developmental trajectory as during neuronal differentiation.…”

Section: Discussionsupporting

confidence: 92%

Dynamics of promoter bivalency and RNAP II pausing in mouse stem and differentiated cells

2018

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BackgroundMammalian embryonic stem cells display a unique epigenetic and transcriptional state to facilitate pluripotency by maintaining lineage-specification genes in a poised state. Two epigenetic and transcription processes involved in maintaining poised state are bivalent chromatin, characterized by the simultaneous presence of activating and repressive histone methylation marks, and RNA polymerase II (RNAPII) promoter proximal pausing. However, the dynamics of histone modifications and RNAPII at promoters in diverse cellular contexts remains underexplored.ResultsWe collected genome wide data for bivalent chromatin marks H3K4me3 and H3K27me3, and RNAPII (8WG16) occupancy together with expression profiling in eight different cell types, including ESCs, in mouse. The epigenetic and transcription profiles at promoters grouped in over thirty clusters with distinct functional identities and transcription control.ConclusionThe clustering analysis identified distinct bivalent clusters where genes in one cluster retained bivalency across cell types while in the other were mostly cell type specific, but neither showed a high RNAPII pausing. We noted that RNAPII pausing is more associated with active genes than bivalent genes in a cell type, and was globally reduced in differentiated cell types compared to multipotent.Electronic supplementary materialThe online version of this article (10.1186/s12861-018-0163-7) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Dynamics of promoter bivalency and RNAP II pausing in mouse stem and differentiated cells

2018

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“…RNA Polymerase II (RNAPII) pausing at genes that are highly inducible has been hypothesized to play a pivotal role in preparing genes for rapid induction in response to environmental or developmental stimuli. In a number of mammalian cellular contexts, bivalent genes have been shown to have a high density of paused RNA Pol II at the promoter-proximal region compared to genes which are actively transcribed, therefore allowing genes to be maintained in a transcriptionally poised state (Stock et al 2007; Ferrai et al 2017; Liu et al 2017). Paused RNA Pol II can be distinguished from other forms by a phosphorylation at Ser5 (Ser5P) of the YSPTSPS heptad repeat at the C-terminus of the largest subunit of the Pol II complex.…”

Section: Resultsmentioning

confidence: 99%

Epigenetic analyses of planarian stem cells demonstrate conservation of bivalent histone modifications in animal stem cells

Dattani¹,

Kao²,

Mihaylova³

et al. 2017

Preprint

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Planarian flatworms have an indefinite capacity to regenerate missing or damaged body parts owing to a population of pluripotent adult stems cells called neoblasts (NBs). Currently, little is known about the importance of the epigenetic status of NBs and how histone modifications regulate homeostasis and cellular differentiation. We have developed an improved and optimized ChIP-seq protocol for NBs in Schmidtea mediterranea and have generated genome-wide profiles for the active marks H3K4me3 and H3K36me3, and suppressive marks H3K4me1 and H3K27me3. The genome-wide profiles of these marks were found to correlate well with NB gene expression profiles. We found that genes with little transcriptional activity in the NB compartment but which switch on in post-mitotic progeny during differentiation are bivalent, being marked by both H3K4me3 and H3K27me3 at promoter regions. In further support of this hypothesis bivalent genes also have a high level of paused RNA Polymerase II at the promoter-proximal region. Overall, this study confirms that epigenetic control is important for the maintenance of a NB transcriptional program and makes a case for bivalent promoters as a conserved feature of animal stem cells and not a vertebrate specific innovation. By establishing a robust ChIP-seq protocol and analysis methodology, we further promote planarians as a promising model system to investigate histone modification mediated regulation of stem cell function and differentiation.

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“…S3B). Thus, in line with bivalent genes in other cell types (Liu et al, 2017;Williams et al, 2015), RNAPII pausing may not be a central mechanism in the later activation of Kmt2b-target genes in the germline.…”

Section: Bivalent and Monovalent Promoters Are Suppressed By Distinctmentioning

confidence: 99%

“…All the PRC1 components examined (Scml2, Rnf2 and Bmi1) and H2AK119ub were enriched at the bivalent, but not at the monovalent, promoters. In ESCs, RNA polymerase II (RNAPII) pausing has been suggested to be involved in priming of bivalent promoters (Marks et al, 2012;Stock et al, 2007), but recent reports have shown contrasting evidence (Liu et al, 2017;Williams et al, 2015). We investigated this possibility by analyzing the RNAPII enrichment using RNAPII ChIP-seq data in GSCs and found that RNAPII was not highly enriched at bivalent and monovalent TSSs compared with all H3K4me3-marked TSSs (Fig.…”

Section: Bivalent and Monovalent Promoters Are Suppressed By Distinctmentioning

confidence: 99%

Kmt2b conveys monovalent and bivalent H3K4me3 in mouse spermatogonial stem cells at germline and embryonic promoters

et al. 2018

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The mammalian male germline is sustained by a pool of spermatogonial stem cells (SSCs) that can transmit both genetic and epigenetic information to offspring. However, the mechanisms underlying epigenetic transmission remain unclear. The histone methyltransferase Kmt2b is highly expressed in SSCs and is required for the SSC-to-progenitor transition. At the stem-cell stage, Kmt2b catalyzes H3K4me3 at bivalent H3K27me3-marked promoters as well as at promoters of a new class of genes lacking H3K27me3, which we call monovalent. Monovalent genes are mainly activated in late spermatogenesis, whereas most bivalent genes are mainly not expressed until embryonic development. These data suggest that SSCs are epigenetically primed by Kmt2b in two distinguishable ways for the upregulation of gene expression both during the spermatogenic program and through the male germline into the embryo. Because Kmt2b is also the major H3K4 methyltransferase for bivalent promoters in embryonic stem cells, we also propose that Kmt2b has the capacity to prime stem cells epigenetically.

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Dynamics of RNA Polymerase II Pausing and Bivalent Histone H3 Methylation during Neuronal Differentiation in Brain Development

Cited by 49 publications

References 48 publications

Dynamics of promoter bivalency and RNAP II pausing in mouse stem and differentiated cells

Dynamics of promoter bivalency and RNAP II pausing in mouse stem and differentiated cells

Epigenetic analyses of planarian stem cells demonstrate conservation of bivalent histone modifications in animal stem cells

Kmt2b conveys monovalent and bivalent H3K4me3 in mouse spermatogonial stem cells at germline and embryonic promoters

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