Glis1 facilitates induction of pluripotency via an epigenome–metabolome–epigenome signalling cascade

Li, Linpeng; Chen, Keshi; Wang, Tianyu; Wu, Yi; Xing, Guangsuo; Chen, Mengqi; Hao, Zhihong; Zhang, Cheng; Zhang, Jinye; Ma, Bochao; Liu, Zihuang; Yuan, Hao; Long, Qi; Zhou, Yanshuang; Qi, Juntao; Zhao, Danyun; Gao, Mengting; Pei, Duanqing; Nie, Jinfu; Ye, Dan; Pan, Guangjin; Liu, Xingguo

doi:10.1038/s42255-020-0267-9

Cited by 129 publications

(79 citation statements)

References 49 publications

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“…H3K18la has been demonstrated to regulate M1 macrophage polarization, cell reprograming and tumorigenesis recently [5,7,8], however, we still don't know how H3K18la is regulated and co-operates with other histone lysine acylations during neural cell fate determination. To this end, we treated differentiating P19 EC cells with MS-275, and performed ChIP-seq assays of H3K9ac, H3K9cr and H3K18la subsequently.…”

Section: Multiple Histone Lysine Acylations Are Implicated In the Upregulation Of Neural Differentiation-related Genes By Ms-275mentioning

confidence: 99%

“…Some metabolites have recently been reported as donors for histone PTMs to influence gene expression, including propionyl-CoA, butyl-CoA, crotonyl-CoA, lactyl-CoA, 2-hydroxyisobutyl-CoA, β-hydroxybutyryl-CoA, malonyl-CoA, succinyl-CoA and glutaryl-CoA [1,3]. Of these, crotonyl-CoA and lactyl-CoA, which act as substrates for histone lysine crotonylation (Kcr) and lysine lactylation (Kla) reactions catalysed by p300/CBP respectively [4,5], have attracted increasing attention due to their emerging roles in linking cellular metabolism and epigenetic regulation to regulate gene expression, cell state transitions and diseases progression [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…Over the last five years, regulatory mechanisms of histone Kcr have been thoroughly elucidated, including its "writers" (enzymes in charge of catalysing Kcr) [4,10,11], "erasers" (enzymes responsible for removing Kcr) [12][13][14], "readers" (enzymes capable of recognising Kcr) [15][16][17][18], and metabolic regulators (enzymes involving in crotonyl-CoA metabolism) [4,[19][20][21][22][23], which extend our knowledge about versatile functions of histone Kcr. Most recent studies have demonstrated that p300 and glycolysis are major pathways to regulate histone Kla levels, and suggested that H3K18la involves in M1 macrophage polarization, cell reprograming and tumorigenesis [5,7,8]. Both histone Kcr and Kla can directly stimulate transcription in a cell free system [4,5].…”

Section: Introductionmentioning

confidence: 99%

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Dynamic profiling and functional interpretation of histone lysine crotonylation and lactylation during neural development

Dai

et al. 2021

Preprint

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Metabolites such as crotonyl-CoA and lactyl-CoA influence gene expression through covalently modifying histones, known as histone lysine crotonylation (Kcr) and histone lysine lactylation (Kla). However, we do not know their dynamic changes, biological functions and associations with histone lysine acetylation (Kac) in vivo and during development. Here, we profile H3K9ac, H3K9cr and H3K18la in the developing telencephalon, and find that genome-wide alterations of these histone marks collaboratively regulate transcriptome remodelling to favour neural differentiation. We also demonstrate that global histone Kcr and Kla levels are not affected by transcription inhibition. Importantly, we identify HDAC1-3 as novel erasers of H3K18la and furtherly show that a selective inhibitor of HDAC1-3, MS-275 promotes transcriptional programs associated with neural cell fate decisions via H3K18la. Taken together, our results uncover the interplays between histone lysine acylations to regulate gene expression and the differentiation-promoting functions of histone Kcr and Kla during development.

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Section: Multiple Histone Lysine Acylations Are Implicated In the Upregulation Of Neural Differentiation-related Genes By Ms-275mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dynamic profiling and functional interpretation of histone lysine crotonylation and lactylation during neural development

Dai

et al. 2021

Preprint

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“…For example, elevated histone lactylation at reparative macrophage gene loci was found to promote the transition of macrophage from inflammatory to reparatory state in response to microbial ligands and various harmful cues [12]. In addition, Glis1-induced histone lactylation at pluripotency gene loci facilitated somatic cell reprogramming [13]. However, the role of histone lactylation in tumorigenesis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma

et al. 2021

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Background Histone lactylation, a metabolic stress-related histone modification, plays an important role in the regulation of gene expression during M1 macrophage polarization. However, the role of histone lactylation in tumorigenesis remains unclear. Results Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, histone lactylation contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified PER1 and TP53 mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma. Conclusion We reveal the oncogenic role of histone lactylation, thereby providing novel therapeutic targets for ocular melanoma therapy. We also bridge histone modifications with RNA modifications, which provides novel understanding of epigenetic regulation in tumorigenesis.

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“…Cell metabolism has been shown to be closely related to the pluripotency of ESCs ( Gu et al, 2016 ; Li et al, 2020 ). We found OSM upregulates ascorbate and retinol metabolic pathways.…”

Section: Discussionmentioning

confidence: 99%

Oncostatin M Maintains Naïve Pluripotency of mESCs by Tetraploid Embryo Complementation (TEC) Assay

Tian

Liu

et al. 2021

Front. Cell Dev. Biol.

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It has been well established that leukemia inhibitory factor (LIF) is essential for maintaining naïve pluripotency of embryonic stem cells (ESCs). Oncostatin M (OSM) is a member of the IL-6 family of cytokines which share gp130 as a receptor subunit, and the OSM-gp130 complex can recruit either LIF receptor β or OSM receptor β. Here we show that OSM can completely replace LIF to maintain naïve pluripotency of ESCs. Mouse ESCs (mESCs) cultured in the presence of LIF or OSM not only express pluripotency genes at similar levels but also exhibit the same developmental pluripotency as evidenced by the generation of germline competent chimeras, supporting previous findings. Moreover, we demonstrate by tetraploid embryo complementation assay, the most stringent functional test of authentic pluripotency that mESCs cultured in OSM produce viable all-ESC pups. Furthermore, telomere length and telomerase activity, which are also crucial for unlimited self-renewal and genomic stability of mESCs, do not differ in mESCs cultured under OSM or LIF. The transcriptome of mESCs cultured in OSM overall is very similar to that of LIF, and OSM activates Stat3 signaling pathway, like LIF. Additionally, OSM upregulates pentose and glucuronate interconversion, ascorbate and aldarate metabolism, and steroid and retinol metabolic pathways. Although the significance of these pathways remains to be determined, our data shows that OSM can maintain naïve pluripotent stem cells in the absence of LIF.

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Glis1 facilitates induction of pluripotency via an epigenome–metabolome–epigenome signalling cascade

Cited by 129 publications

References 49 publications

Dynamic profiling and functional interpretation of histone lysine crotonylation and lactylation during neural development

Dynamic profiling and functional interpretation of histone lysine crotonylation and lactylation during neural development

Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma

Oncostatin M Maintains Naïve Pluripotency of mESCs by Tetraploid Embryo Complementation (TEC) Assay

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