The histone demethylase <scp>PHF</scp>8 facilitates alternative splicing of the histocompatibility antigen <scp>HLA</scp>‐G

Leisegang, Matthias; Gu, Lunda; Preussner, Jens; Günther, Stefan; Hitzel, Juliane; Ratiu, Corina; Weigert, Andreas; Chen, Wei; Schwarz, Eva C.; Looso, Mario; Fork, Christian; Brandes, Ralf P.

doi:10.1002/1873-3468.13337

Cited by 6 publications

(5 citation statements)

References 42 publications

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“…Histone methylation is important in chromatin packaging and gene expression and has been proven to be involved in the regulation of inflammatory processes and osteogenic differentiation 24,25 . As a histone demethylase, PHF8 regulates the methylation states of various histone lysine residues, thus modulating gene expression 26 . PHF8 also mediates inflammatory processes 15 and plays an important role in the development of craniomaxillofacial bone by regulating the methylation of histone sites H4K20 and H3K9 10 .…”

Section: Discussionmentioning

confidence: 99%

The role of PHF8 and TLR4 in osteogenic differentiation of periodontal ligament cells in inflammatory environment

Liu

et al. 2020

Journal of Periodontology

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Background: Histone methylation is considered to play an important role in the occurrence and development of periodontitis. Plant homeodomain finger protein 8 (PHF8), a histone demethylase, has been shown to regulate inflammation and osteogenic differentiation of bone marrow stromal cells (BMSCs). This study aimed to detect the functions of PHF8 and TLR4 in osteogenic differentiation in an inflammatory environment induced by Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) Methods: A periodontitis mouse model was established, and the mice were treated with TAK-242. Immunohistochemical staining was used to detect the expression of PHF8 in periodontal tissue. Periodontal ligament cells (PDLCs) were treated with mineralization induction medium supplemented with Pg-LPS and/or TAK-242, and a Cell Counting Kit-8 (CCK-8) assay was used to detect the proliferation of PDLCs. Real-time PCR and western blotting were used to detect the mRNA and protein expression levels, respectively, of PHF8, toll-like receptor 4 (TLR4) and the other osteogenic markers alkaline phosphatase (ALP), osteocalcin (OCN), Special AT-rich sequence-binding protein 2 (Satb2) and Runt-related transcription factor 2 (Runx2) Results: Periodontitis reduced PHF8 expression in periodontal tissue, and TAK-242 partially reversed this downregulation. An in vitro experiment revealed that the mRNA and protein expression levels of PHF8 were significantly upregulated during the osteogenic differentiation of PDLCs. Alizarin red staining showed that the mineralized nodules of PDLCs in osteogenic induction group were more than those in control group. Real-time PCR and western blot results indicated that Pg-LPS inhibited PHF8 expression and upregulated TLR4 expression in PDLCs.TAK-242 inhibited TLR4 and partially reversed the inhibition of PHF8 expression and osteogenic differentiation induced by Pg-LPS in PDLCs Conclusion: PHF8 and TLR4 play important roles in periodontitis. Pg-LPS inhibits the expression of PHF8 via upregulation of TLR4 and might further inhibit the osteogenic differentiation of PDLCs. However, the specific mechanisms involved remain to be explored.

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Section: Discussionmentioning

confidence: 99%

The role of PHF8 and TLR4 in osteogenic differentiation of periodontal ligament cells in inflammatory environment

Liu

et al. 2020

Journal of Periodontology

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“…However, unlike other HLA Class I molecules incapable of producing soluble isoforms, it is still unknown why a premature stop codon, located in intron 4 of the HLA-G gene, is matured in EVTs only leading to create soluble HLA-G isoforms. According to the recent study [29], depletion of PHF 8 (Plant Homeodomain Finger protein 8), a histone demethylase of H3K9 (lysine residue 9 on histone H3), in HUVECs (Human umbilical vein endothelial cells) and JEG3 cells, led to increased H3K9me2 (dimethylated state of H3K9) levels within intron 4 of the HLA-G gene. Consequently, the stop codon located in intron 4 of the HLA-G gene is matured to terminate the transcription process, increasing the expression of soluble HLA-G5/6 mRNAs containing intron 4.…”

Section: Progesterone Induced By In-vivo Like Temperature Change Mamentioning

confidence: 99%

Study of immune‐tolerized cell lines and extracellular vesicles inductive environment promoting continuous expression and secretion of HLA‐G from semiallograft immune tolerance during pregnancy

Cho¹,

Kook²,

Kang³

et al. 2020

J of Extracellular Vesicle

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An immune reaction is a protector of our body but a target to be overcome for all non-self-derived medicine. Extracellular Vesicles (EVs), noted as a primary alternative to cell therapy products that exhibit immune rejection due to mismatching-major histocompatibility complex (MHC), were discovered to have excellent curative effects through the delivery of various biologically active substances. Although EVs are sure to incur immune reaction by immunogenicity due to alloantigens from their parental cells, their immune rejection is rarely known. Hence, to develop cell lines and EVs as medicines with no immune rejection, we noted the immune tolerance where the foetus, as semiallograft, is perfectly protected from the maternal immune system. We designed the ex-vivo culture systems to simulate in-vivo environmental factors inducing extravillous trophoblast (EVT)-specific Human Leukocyte Antigen-G (HLA-G) expression and secretion of HLA-G-bearing EVs at the motherfoetus interface. Using them, we confirmed that immune-tolerized stem cells (itSCs) continuously expressing and secreting HLA-G like EVTs during pregnancy can be induced. Also, EVs secreted from itSCs are verified as immune-tolerized EVs (itSC-EVs) containing HLA-G and not causing immune rejection through various analytical methods. These findings can provide a new perspective on the local and extensive immune tolerance environment where HLA-G is expressed and secreted by pregnancy-related hormones and different biological conditions. Furthermore, they show the new way to develop itSCs-EVs-based therapeutics that are free from time, space, and donor limitation causing immune rejection.

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“…Histone methyltransferases and demethylases allow the activation of the promoter (H3 4-trimethyl lysine), enhancer activity (H3K4me1), or repression (H3K9me2 / 3, H3K27me2 / 3) [35]. The catalytic role of KDM7 members in the demethylation of repressive histone markers such as H3K9me1 / 2, H3K27me1 / 2, or H4K20me1 is characterized by marked differences in substrate specificity between different enzymes [36,37].…”

Section: Discussionmentioning

confidence: 99%

Study of the expression of genes associated with post-translational changes in histones in the internal thoracic artery and the saphenous vein grafts used in coronary artery bypass grafting procedure

Kałużna

Nawrocki

Bryl

et al. 2020

Medical Journal of Cell Biology

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Coronary artery disease (CAD) is one of the leading causes of mortality in the world. The most advanced forms of CAD are usually treated by means of coronary artery bypass grafting (CABG). The selection of the appropriate vessels as aortocoronary conduits is of paramount importance. The internal thoracic artery (ITA) or the great saphenous vein (SV) are often harvested. Furthermore, epigenetic processes have been recently associated with atherosclerosis, hypertension, and heart failure, and post-translational histone processes may play a key role in understanding the genetic predisposition of vessels to vascular diseases.In the experiment performed, the transcript levels of JHDM1D, PHF8, and HDAC 1-3 in SV and ITA used for CABG procedures with RT-qPCR were examined. Total RNA was isolated by the method of Chomczyński and Sachi. RNA samples were reverse transcribed into cDNA using a commercial kit. The determination of the level of the transcripts of the mentioned genes was performed using the Light Cycler® 96 Real-Time PCR kit. Our analyzes confirmed that the studied genes related to post-translational modifications of histones are expressed in SV and ITA. In the saphenous vein, the expression of each of the individual genes was higher. The most considerable difference in transcript levels was recorded for HDAC1 and the smallest difference in expression for HDAC2.Our research suggests that more processes related to histone demethylation and acetylation occur in the saphenous vein, which may affect the selection of a vessel for CABG, but this research requires more research and additional analysis.Running title: Histone regulating gene expression in common coronary artery bypass graft vessels

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The histone demethylase PHF8 facilitates alternative splicing of the histocompatibility antigen HLA‐G

Cited by 6 publications

References 42 publications

The role of PHF8 and TLR4 in osteogenic differentiation of periodontal ligament cells in inflammatory environment

The role of PHF8 and TLR4 in osteogenic differentiation of periodontal ligament cells in inflammatory environment

Study of immune‐tolerized cell lines and extracellular vesicles inductive environment promoting continuous expression and secretion of HLA‐G from semiallograft immune tolerance during pregnancy

Study of the expression of genes associated with post-translational changes in histones in the internal thoracic artery and the saphenous vein grafts used in coronary artery bypass grafting procedure

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