JMJD1B, a novel player in histone H3 and H4 processing to ensure genome stability

Saavedra, Francisco; Gurard-Levin, Zachary A.; Rojas-Villalobos, Camila; Vassias, Isabelle; Quatrini, Raquel; Almouzni, Geneviève; Loyola, Alejandra

doi:10.1186/s13072-020-00331-1

Cited by 11 publications

(5 citation statements)

References 35 publications

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“…We initially obtained clones that were degron tagged at both Kdm3b alleles with decreased expression of the KDM3B protein (Figure 2B). Even though depletion of KDM3B has been shown in some cases to lead to genome instability (73), importantly, these clones maintained a stable karyotype throughout the derivation process (Supplementary Figure S2C). The Kdm3b-degron tagged clones were then targeted with the Kdm3a degron construct and heterozygous clones were obtained where one allele of Kdm3a codes for an in-frame degron tag and the second allele was knocked-out by an insertion at the 3’ repair site (Supplementary Figure S2B and D).…”

Section: Resultsmentioning

confidence: 99%

KDM3A and KDM3B Maintain Naïve Pluripotency Through the Regulation of Alternative Splicing

Dillingham

Cormaty

Morgan

et al. 2023

Preprint

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Histone modifying enzymes play a central role in maintaining cell identity by establishing a conducive chromatin environment for lineage specific transcription factor activity. Pluripotent embryonic stem cells (ESCs) identity is characterized by lower abundance of gene repression associated histone modifications that enables rapid response to differentiation cues. The KDM3 histone demethylase family removes the repressive histone H3 lysine 9 dimethylation (H3K9me2). Here we uncover a surprising role for the KDM3 proteins in the maintenance of the pluripotent state through post-transcriptional regulation. We find through immunoaffinity purification of the KDM3A or KDM3B interactome and proximity ligation assays that KDM3A and KDM3B interact with RNA processing factors such as EFTUD2 and PRMT5. By generating double degron ESCs to degrade KDM3A and KDM3B in the rapid timescale of splicing, we find altered splicing, independent of H3K9me2 status. These splicing changes partially resemble the splicing pattern of the more blastocyst-like ground state of pluripotency and occurred in important chromatin and transcription factors such as Dnmt3b, Tbx3 and Tcf12. Our findings reveal non-canonical roles of histone modifying enzymes in splicing to regulate cell identity.

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Section: Resultsmentioning

confidence: 99%

KDM3A and KDM3B Maintain Naïve Pluripotency Through the Regulation of Alternative Splicing

Dillingham

Cormaty

Morgan

et al. 2023

Preprint

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show abstract

“…We also identified ubiquitin degradation pathway-associated proteins UAB14, UBC4, and UCN2. NASP is regulated by the ubiquitin-proteasome pathway in HeLa cells [ 53 ]. In addition, the spindle assembled proteins SAS6A, acetyltransferase Atp, and ELP3 were also found in the complexes (Fig.…”

Section: Resultsmentioning

confidence: 99%

The histone chaperone Nrp1 is required for chromatin stability and nuclear division in Tetrahymena thermophila

Lian

Hao

et al. 2021

Epigenetics & Chromatin

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Histone chaperones facilitate DNA replication and repair by promoting chromatin assembly, disassembly and histone exchange. Following histones synthesis and nucleosome assembly, the histones undergo posttranslational modification by different enzymes and are deposited onto chromatins by various histone chaperones. In Tetrahymena thermophila, histones from macronucleus (MAC) and micronucleus (MIC) have been comprehensively investigated, but the function of histone chaperones remains unclear. Histone chaperone Nrp1 in Tetrahymena contains four conserved tetratricopepeptide repeat (TPR) domains and one C-terminal nuclear localization signal. TPR2 is typically interrupted by a large acidic motif. Immunofluorescence staining showed that Nrp1 is located in the MAC and MICs, but disappeared in the apoptotic parental MAC and the degraded MICs during the conjugation stage. Nrp1 was also colocalized with α-tubulin around the spindle structure. NRP1 knockdown inhibited cellular proliferation and led to the loss of chromosome, abnormal macronuclear amitosis, and disorganized micronuclear mitosis during the vegetative growth stage. During sexual developmental stage, the gametic nuclei failed to be selected and abnormally degraded in NRP1 knockdown mutants. Affinity purification combined with mass spectrometry analysis indicated that Nrp1 is co-purified with core histones, heat shock proteins, histone chaperones, and DNA damage repair proteins. The physical direct interaction of Nrp1 and Asf1 was also confirmed by pull-down analysis in vitro. The results show that histone chaperone Nrp1 is involved in micronuclear mitosis and macronuclear amitosis in the vegetative growth stage and maintains gametic nuclei formation during the sexual developmental stage. Nrp1 is required for chromatin stability and nuclear division in Tetrahymena thermophila.

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“…A recent study corroborates the link between testicular NASP (tNASP) and newly synthesized histones H3 and H4. Specifically, reduction of JMJD1B (histone demethylase) increases the expression levels of tNASP which leads to the accumulation of histones H3 and H4 at the early phase of their maturation [49]. Although it has a low degree of homology with the budding yeast protein Hat1interacting factor 1 (Hif1) [50], both are able to bind the H3/H4 heterodimer [43].…”

Section: Cellular Localization and Function Of Hat1mentioning

confidence: 99%

Recent insights intoHistone Acetyltransferase-1: biological function and involvement in pathogenesis

et al. 2020

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Acetylation of histone and non-histone proteins is a post-translational modification mostly associated with activation of gene transcription. The first histone acetyltransferase (HAT) identified as modifying newly synthesized histone H4 in yeast was a type B HAT named HAT1. Although it was the first HAT to be discovered, HAT1 remains one of the most poorly studied enzymes in its class. In addition to its well-established role in the cytoplasm, recent findings have revealed new and intriguing aspects of the function of HAT1 in the nucleus. Several studies have described its involvement in regulating different pathways associated with a wide range of diseases, including cancer. This review focuses on our current understanding of HAT1, highlighting its importance in regulating chromatin replication and gene expression. This previously unknown role for HAT1 opens up novel scenarios in which further studies will be required to better understand its function.

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JMJD1B, a novel player in histone H3 and H4 processing to ensure genome stability

Cited by 11 publications

References 35 publications

KDM3A and KDM3B Maintain Naïve Pluripotency Through the Regulation of Alternative Splicing

KDM3A and KDM3B Maintain Naïve Pluripotency Through the Regulation of Alternative Splicing

The histone chaperone Nrp1 is required for chromatin stability and nuclear division in Tetrahymena thermophila

Recent insights intoHistone Acetyltransferase-1: biological function and involvement in pathogenesis

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