JMJD3: a critical epigenetic regulator in stem cell fate

Ding, Yuanjie; Yao, Yuanchun; Xing-mu, Gong; Zhuo, Qin; Chen, Jinhua; Tian, Miao; Farzaneh, Maryam

doi:10.1186/s12964-021-00753-8

Cited by 22 publications

(12 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To do that, SMAD2/3, the major effectors of the pathway, cooperate with specific cofactors to regulate transcription. Particularly, SMAD3 interacts with the lysine demethylase (KDM) JMJD3 23 , 27 , 28 , a Jumonji C (JmjC) domain-containing enzyme that catalyzes the histone 3 lysine 27 trimethylation (H3K27me3) removal 29 , 30 and has been linked to numerous developmental processes (reviewed in 31 , 32 ). In cortical progenitor cells, we have previously shown that JMJD3 cooperates with the TGFβ pathway to induce neuronal differentiation 23 , 33 .…”

Section: Introductionmentioning

confidence: 99%

JMJD3 intrinsically disordered region links the 3D-genome structure to TGFβ-dependent transcription activation

et al. 2022

View full text Add to dashboard Cite

Enhancers are key regulatory elements that govern gene expression programs in response to developmental signals. However, how multiple enhancers arrange in the 3D-space to control the activation of a specific promoter remains unclear. To address this question, we exploited our previously characterized TGFβ-response model, the neural stem cells, focusing on a ~374 kb locus where enhancers abound. Our 4C-seq experiments reveal that the TGFβ pathway drives the assembly of an enhancer-cluster and precise gene activation. We discover that the TGFβ pathway coactivator JMJD3 is essential to maintain these structures. Using live-cell imaging techniques, we demonstrate that an intrinsically disordered region contained in JMJD3 is involved in the formation of phase-separated biomolecular condensates, which are found in the enhancer-cluster. Overall, in this work we uncover novel functions for the coactivator JMJD3, and we shed light on the relationships between the 3D-conformation of the chromatin and the TGFβ-driven response during mammalian neurogenesis.

show abstract

Section: Introductionmentioning

confidence: 99%

JMJD3 intrinsically disordered region links the 3D-genome structure to TGFβ-dependent transcription activation

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Studies of human monocytes trained by exposure to β-glucan showed that they accumulate fumarate (a metabolite of tricarboxylic acid cycle (TCA)), which downregulates histone demethylase KDM5. Another TCA metabolite, the αketoglutarate, mediates epigenetic reprograming through the histone demethylase Jumonji domain-containing protein-3 (JMJD3) that regulates trimethylation of histone H3 on lysine 27 [60,75].…”

Section: Molecular Signature and Markers Of Memory Monocytes/macrophagesmentioning

confidence: 99%

Memory Macrophages

Kloc

Kubiak

Zdanowski³

et al. 2022

IJMS

View full text Add to dashboard Cite

Immunological memory is a crucial part of the immune defense that allows organisms to respond against previously encountered pathogens or other harmful factors. Immunological memory is based on the establishment of epigenetic modifications of the genome. The ability to memorize encounters with pathogens and other harmful factors and mount enhanced defense upon subsequent encounters is an evolutionarily ancient mechanism operating in all animals and plants. However, the term immunological memory is usually restricted to the organisms (invertebrates and vertebrates) possessing the immune system. The mammalian immune system, with innate and adaptive branches, is the most sophisticated among vertebrates. The concept of innate memory and memory macrophages is relatively new and thus understudied. We introduce the concept of immunological memory and describe types of memory in different species and their evolutionary status. We discuss why the traditional view of innate immune cells as the first-line defenders is too restrictive and how the innate immune cells can accumulate and retain immunologic memory. We describe how the initial priming leads to chromatin remodeling and epigenetic changes, which allow memory macrophage formation. We also summarize what is currently known about the mechanisms underlying development of memory macrophages; their molecular and metabolic signature and surface markers; and how they may contribute to immune defense, diseases, and organ transplantation.

show abstract

“…However, little information is available about the underlying mechanism of MALAT1 in regulating the odontoblastic differentiation of hDPSCs. Jumonji domain‐containing 3 (JMJD3) is a histone demethylase with substrate specificity for catalysing the removal of histone 3 lysine 27 trimethylation (H3K27me3), which is a gene silencing mark (Ding et al, 2021). Several studies have demonstrated that JMJD3 promotes odontogenic differentiation by removing H3K27me3 silencing marks on differentiation‐related gene promoters in dental‐derived MSCs (Hoang et al, 2016; Xu et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

The ATF4‐regulated LncRNA MALAT1 promotes odontoblastic differentiation of human dental pulp stem cells via histone demethylase JMJD3: An in vitro study

Yu,

Guo,

Yang

et al. 2023

Int Endodontic J

View full text Add to dashboard Cite

AimThis study aimed to investigate the upstream regulators and specific mechanisms of metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) in the odontoblastic differentiation of human dental pulp stem cells (hDPSCs).MethodologyHuman dental pulp stem cells were isolated and cultured, followed by conducting loss‐ or gain‐of‐function experiments on ATF4 and loss experiments on MALAT1 to elucidate their respective biological functions in odontoblastic differentiation. Chromatin immunoprecipitation assays and RNA immunoprecipitation were performed to uncover the interaction between ATF4‐MALAT1 and MALAT1‐JMJD3, respectively. The odontoblastic differentiation was estimated by the mRNA and protein of DSPP and DMP1, as well as alkaline phosphatase staining.ResultsExpression of MALAT1 was upregulated in the hDPSCs cultured in an odontoblastic medium, and MALAT1 downregulation suppressed the odontoblastic differentiation of the hDPSCs. Subsequent experiments confirmed that ATF4 promoted odontoblastic differentiation and induced MALAT1 expression by binding to the MALAT1 promoter region. Further experiments revealed that nuclear MALAT1 interacted with JMJD3. MALAT1 knockdown decreased the JMJD3 protein level and demethylase activity, and it enhanced H3K27me3 occupancy of the promoter region of DSPP and DMP1, resulting in the inhibition of DSPP and DMP1 transcription. Importantly, JMJD3 overexpression significantly attenuated the inhibition of odontoblastic differentiation induced by MALAT1 knockdown.ConclusionsATF4‐regulated MALAT1 plays a positive regulatory role in odontoblastic differentiation of hDPSCs through JMJD3‐mediated H3K27me3 modifications of the DSPP and DMP1 promoters.

show abstract

JMJD3: a critical epigenetic regulator in stem cell fate

Cited by 22 publications

References 110 publications

JMJD3 intrinsically disordered region links the 3D-genome structure to TGFβ-dependent transcription activation

JMJD3 intrinsically disordered region links the 3D-genome structure to TGFβ-dependent transcription activation

Memory Macrophages

The ATF4‐regulated LncRNA MALAT1 promotes odontoblastic differentiation of human dental pulp stem cells via histone demethylase JMJD3: An in vitro study

Contact Info

Product

Resources

About