Histone deacetylase 3 is selectively involved in L3MBTL2-mediated transcriptional repression

Yoo, Jung-Yoon,Choi, Kyung-Chul,Kang, HeeBum,Kim, Young Jun,Lee, Jeongmin,Jun, Woo Jin,Kim, Mi-Jeong,Lee, Yoo-Hyun,Lee, Ok-Hee,Yoon, Ho-Geun Elsevier 2010 FEBS letters Vol.584 No.11

<P><B>Abstract</B></P><P>This is the first report that L(3)mbt-like 2 (L3MBTL2) specifically interacts with the histone deacetylase domain of histone deacetylase 3 (HDAC3) via its MBT domain. Here, we show that L3MBTL2 selectively interacts with HDAC3, but not other class I HDACs. An in vitro peptide-binding assay demonstrated the specific association of HDAC3 with methylated histone-K20 tail and L3MBTL2. Furthermore, depletion of HDAC3 resulted in a decrease of methylated K20-H4, as well as an increase in acetylated histone H3. Consequently, HDAC3 knock-down selectively suppressed L3MBTL2-mediated transcriptional repression. Taken together, our results reveal the concerted action of both HDAC3 and L3MBTL2 in histone deacetylation and methylation-dependent transcriptional repression.</P><P><B>Structured summary</B></P><P>MINT-7719975: <I>L3MBTL2</I> (uniprotkb:Q969R5) and <I>HDAC3</I> (uniprotkb:O15379) <I>colocalize</I> (MI:0403) by <I>fluorescence microscopy</I> (MI:0416)</P><P>MINT-7719941, MINT-7719921: <I>L3MBTL2</I> (uniprotkb:Q969R5) <I>binds</I> (MI:0407) to <I>HDAC3</I> (uniprotkb:O15379) by <I>pull down</I> (MI:0096)</P><P>MINT-7719991: <I>HDAC3</I> (uniprotkb:O15379) <I>physically interacts</I> (MI:0915) with <I>L3MBTL2</I> (uniprotkb:Q969R5) by <I>anti bait coimmunoprecipitation</I> (MI:0006)</P><P>MINT-7719958: <I>L3MBTL2</I> (uniprotkb:Q969R5) <I>physically interacts</I> (MI:0915) with <I>HDAC3</I> (uniprotkb:O15379) by <I>anti tag coimmunoprecipitation</I> (MI:0007)</P><P>MINT-7719897: <I>HDAC3</I> (uniprotkb:O15379) <I>physically interacts</I> (MI:0915) with <I>L3MBTL2</I> (uniprotkb:Q969R5) by <I>two hybrid</I> (MI:0018)</P>

Histone Acetylation in Fungal Pathogens of Plants

Jeon, Junhyun,Kwon, Seomun,Lee, Yong-Hwan The Korean Society of Plant Pathology 2014 Plant Pathology Journal Vol.30 No.1

Acetylation of histone lysine residues occurs in different organisms ranging from yeast to plants and mammals for the regulation of diverse cellular processes. With the identification of enzymes that create or reverse this modification, our understanding on histone acetylation has expanded at an amazing pace during the last two decades. In fungal pathogens of plants, however, the importance of such modification has only just begun to be appreciated in the recent years and there is a dearth of information on how histone acetylation is implicated in fungal pathogenesis. This review covers the current status of research related to histone acetylation in plant pathogenic fungi and considers relevant findings in the interaction between fungal pathogens and host plants. We first describe the families of histone acetyltransferases and deacetylases. Then we provide the cases where histone acetylation was investigated in the context of fungal pathogenesis. Finally, future directions and perspectives in epigenetics of fungal pathogenesis are discussed.

Is There a Link Between Expression Levels of Histone Deacetylase/Acetyltransferase in Mouse Sperm and Subsequent Blastocyst Development?

Kim, Jayeon,Kim, Ji-Hee,Jee, Byung-Chul,Suh, Chang-Suk,Kim, Seok-Hyun SAGE Publications 2015 REPRODUCTIVE SCIENCES Vol.22 No.11

<P>Histone acetylation has been known to be significant in spermatogenesis. Histone acetylation is regulated by the act of histone deacetylases (HDACs) and histone acetyltransferases (HATs). We investigated the link between expression levels of HDACs and HATs in mouse sperm and subsequent blastocyst formation rate. In the univariate analysis, expression levels of HDAC1 and HAT were generally not associated with the blastocyst formation rate. When divided by the mature oocyte number category, a significant positive association was observed between the expression levels of HDAC1 and the blastocyst-forming rate in the highest (> 75th) percentile group (a group with 34 mature oocytes). In conclusion, expression of sperm HDAC1 could be considered as a possible predictor of embryo development in mice with high ovarian response.</P>

Histone Acetylation in Fungal Pathogens of Plants

전준현,권서문,이용환 한국식물병리학회 2014 Plant Pathology Journal Vol.30 No.1

Acetylation of histone lysine residues occurs in differentorganisms ranging from yeast to plants and mammalsfor the regulation of diverse cellular processes. Withthe identification of enzymes that create or reverse thismodification, our understanding on histone acetylationhas expanded at an amazing pace during the last twodecades. In fungal pathogens of plants, however, theimportance of such modification has only just begun tobe appreciated in the recent years and there is a dearthof information on how histone acetylation is implicatedin fungal pathogenesis. This review covers the currentstatus of research related to histone acetylation inplant pathogenic fungi and considers relevant findingsin the interaction between fungal pathogens andhost plants. We first describe the families of histoneacetyltransferases and deacetylases. Then we providethe cases where histone acetylation was investigatedin the context of fungal pathogenesis. Finally, futuredirections and perspectives in epigenetics of fungalpathogenesis are discussed.

Microbial short-chain fatty acids: a bridge between dietary fibers and poultry gut health — A review

Ali Qasim,Ma Sen,La Shaokai,Guo Zhiguo,Liu Boshuai,Gao Zimin,Farooq Umar,Wang Zhichang,Zhu Xiaoyan,Cui Yalei,Li Defeng,Shi Yinghua 아세아·태평양축산학회 2022 Animal Bioscience Vol.35 No.10

The maintenance of poultry gut health is complex depending on the intricate balance among diet, the commensal microbiota, and the mucosa, including the gut epithelium and the superimposing mucus layer. Changes in microflora composition and abundance can confer beneficial or detrimental effects on fowl. Antibiotics have devastating impacts on altering the landscape of gut microbiota, which further leads to antibiotic resistance or spread the pathogenic populations. By eliciting the landscape of gut microbiota, strategies should be made to break down the regulatory signals of pathogenic bacteria. The optional strategy of conferring dietary fibers (DFs) can be used to counterbalance the gut microbiota. DFs are the non-starch carbohydrates indigestible by host endogenous enzymes but can be fermented by symbiotic microbiota to produce shortchain fatty acids (SCFAs). This is one of the primary modes through which the gut microbiota interacts and communicate with the host. The majority of SCFAs are produced in the large intestine (particularly in the caecum), where they are taken up by the enterocytes or transported through portal vein circulation into the bloodstream. Recent shreds of evidence have elucidated that SCFAs affect the gut and modulate the tissues and organs either by activating G-protein-coupled receptors or affecting epigenetic modifications in the genome through inducing histone acetylase activities and inhibiting histone deacetylases. Thus, in this way, SCFAs vastly influence poultry health by promoting energy regulation, mucosal integrity, immune homeostasis, and immune maturation. In this review article, we will focus on DFs, which directly interact with gut microbes and lead to the production of SCFAs. Further, we will discuss the current molecular mechanisms of how SCFAs are generated, transported, and modulated the pro-and anti-inflammatory immune responses against pathogens and host physiology and gut health. The maintenance of poultry gut health is complex depending on the intricate balance among diet, the commensal microbiota, and the mucosa, including the gut epithelium and the superimposing mucus layer. Changes in microflora composition and abundance can confer beneficial or detrimental effects on fowl. Antibiotics have devastating impacts on altering the landscape of gut microbiota, which further leads to antibiotic resistance or spread the pathogenic populations. By eliciting the landscape of gut microbiota, strategies should be made to break down the regulatory signals of pathogenic bacteria. The optional strategy of conferring dietary fibers (DFs) can be used to counterbalance the gut microbiota. DFs are the non-starch carbohydrates indigestible by host endogenous enzymes but can be fermented by symbiotic microbiota to produce shortchain fatty acids (SCFAs). This is one of the primary modes through which the gut microbiota interacts and communicate with the host. The majority of SCFAs are produced in the large intestine (particularly in the caecum), where they are taken up by the enterocytes or transported through portal vein circulation into the bloodstream. Recent shreds of evidence have elucidated that SCFAs affect the gut and modulate the tissues and organs either by activating G-protein-coupled receptors or affecting epigenetic modifications in the genome through inducing histone acetylase activities and inhibiting histone deacetylases. Thus, in this way, SCFAs vastly influence poultry health by promoting energy regulation, mucosal integrity, immune homeostasis, and immune maturation. In this review article, we will focus on DFs, which directly interact with gut microbes and lead to the production of SCFAs. Further, we will discuss the current molecular mechanisms of how SCFAs are generated, transported, and modulated the pro-and anti-inflammatory immune responses against pathogens and host physiology and gut health.

Isotype-Specific Inhibition of Histone Deacetylases: Identification of Optimal Targets for Radiosensitization

Kim, Jin Ho,Moon, Sung Ho,No, Mina,Kim, Jae Jin,Choi, Eun Jung,Cho, Bong Jun,Kim, Jae Sung,Kim, Il Han,Kim, In Ah 대한암학회 2016 Cancer Research and Treatment Vol.48 No.3

<P><B>Purpose</B></P><P>Histone deacetylase (HDAC) inhibitors radiosensitize tumor cells. To elucidate mechanisms underlying radiosensitization by HDAC inhibition, understanding of differential contributions of HDAC isotypes is needed. The aim of this study was to investigate involvement of known HDAC isotypes in modulation of cellular radiosensitivity.</P><P><B>Materials and Methods</B></P><P>Because pharmacologic HDAC inhibitors lack isotype-specificity, RNA interference against 11 HDAC isotypes was used to inhibit HDAC in an isotype-specific manner. Radiation cell survival was evaluated using a clonogenic assay in SQ20B cells transfected with small interfering RNA specifically targeting HDAC isotypes. Immunocytochemistry was performed for detection of γH2AX foci. Protein expression was measured using Western blotting.</P><P><B>Results</B></P><P>Among 11 HDAC isotypes tested, specific inhibition of 7 isotypes (HDAC1, HDAC3, HDAC4, HDAC6, HDAC7, HDAC10, and HDAC11) enhanced radiation lethality in SQ20B cells. Radiosensitization by inhibition of these HDAC isotypes was accompanied by delay of DNA double strand break repair. Radiosensitivity of SQ20B cells was not altered by selective inhibition of the remaining four isotypes (HDAC2, HDAC5, HDAC8, and HDAC9). Inhibition of HDAC isotypes resulted in downregulation of various proteins involved in pro-survival and DNA damage repair pathways.</P><P><B>Conclusion</B></P><P>Isotype-specificity exists in HDAC inhibition-induced radiosensitization. Different HDAC isotypes are differentially involved in modulation of cellular radiosensitivity.</P>

Histone Deacetylase-3 Mediates Positive Feedback Relationship between Anaphylaxis and Tumor Metastasis

Eom, Sangkyung,Kim, Youngmi,Park, Deokbum,Lee, Hansoo,Lee, Yun Sil,Choe, Jongseon,Kim, Young Myeong,Jeoung, Dooil American Society for Biochemistry and Molecular Bi 2014 The Journal of biological chemistry Vol.289 No.17

<P>Allergic inflammation has been known to enhance the metastatic potential of tumor cells. The role of histone deacetylase-3 (HDAC3) in allergic skin inflammation was reported. We investigated HDAC3 involvement in the allergic inflammation-promotion of metastatic potential of tumor cells. Passive systemic anaphylaxis (PSA) induced HDAC3 expression and FcϵRI signaling in BALB/c mice. PSA enhanced the tumorigenic and metastatic potential of mouse melanoma cells in HDAC3- and monocyte chemoattractant protein 1-(MCP1)-dependent manner. The PSA-mediated enhancement of metastatic potential involved the induction of HDAC3, MCP1, and CD11b (a macrophage marker) expression in the lung tumor tissues. We examined an interaction between anaphylaxis and tumor growth and metastasis at the molecular level. Conditioned medium from antigen-stimulated bone marrow-derived mouse mast cell cultures induced the expression of HDAC3, MCP1, and CCR2, a receptor for MCP1, in B16F1 mouse melanoma cells and enhanced migration and invasion potential of B16F1 cells. The conditioned medium from B16F10 cultures induced the activation of FcϵRI signaling in lung mast cells in an HDAC3-dependent manner. FcϵRI signaling was observed in lung tumors derived from B16F10 cells. Target scan analysis predicted HDAC3 to be as a target of miR-384, and miR-384 and HDAC3 were found to form a feedback regulatory loop. miR-384, which is decreased by PSA, negatively regulated HDAC3 expression, allergic inflammation, and the positive feedback regulatory loop between anaphylaxis and tumor metastasis. We show the miR-384/HDAC3 feedback loop to be a novel regulator of the positive feedback relationship between anaphylaxis and tumor metastasis.</P>

Inhibition of Histone Deacetylase 10 Induces Thioredoxin-Interacting Protein and Causes Accumulation of Reactive Oxygen Species in SNU-620 Human Gastric Cancer Cells

Ju-Hee Lee,Eun-Goo Jeong,최문창,Sung-Hak Kim,Jung-Hyun Park,송상현,Jinah Park,방영주,김태유 한국분자세포생물학회 2010 Molecules and cells Vol.30 No.2

Histone deacetylase (HDAC)10, a novel class IIb histone deacetylase, is the most similar to HDAC6, since both con-tain a unique second catalytic domain. Unlike HDAC6, which is located in the cytoplasm, HDAC10 resides in both the nucleus and cytoplasm. The transcriptional targets of HDAC10 that are associated with HDAC10 gene regulation have not been identified. In the present study, we found that knockdown of HDAC10 significantly increased the mRNA expression levels of thioredoxin-interacting protein (TXNIP) in SNU-620 human gastric cancer cells; whereas inhibition of HDAC1, HDAC2, and HDAC6 did not affect TXNIP expression. TXNIP is the endogenous inhibitor of thioredoxin (TRX), which acts as a cellular antioxidant. Real-time PCR and immunoblot analysis confirmed that inhibition of HDAC10 induced TXNIP expression. Com-pared to class I only HDAC inhibitors, inhibitors targeting both class I and II upregulated TXNIP, indicating that TXNIP is regulated by class II HDACs such as HDAC10. We further verified that inhibition of HDAC10 induced release of cyto-chrome c and activated apoptotic signaling molecules through accumulation of reactive oxygen species (ROS). Taken together, our results demonstrate that HDAC10 is involved in transcriptional downregulation of TXNIP, leading to altered ROS signaling in human gastric cancer cells. How TXNIP is preferentially regulated by HDAC10 needs further investigation.

Histone Deacetylase-3 Modification of MicroRNA-31 Promotes Cell Proliferation and Aerobic Glycolysis in Breast Cancer and Is Predictive of Poor Prognosis

Yunfei Zhao,Jiao He,Ling Yang,Qichi Luo,Zhi Liu 한국유방암학회 2018 Journal of breast cancer Vol.21 No.2

Purpose: The incidence and mortality of breast cancer is increasing worldwide. There is a constant quest to understand the underlying molecular biology of breast cancer so as to plan better treatment options. The purpose of the current study was to characterize the expression of histone deacetylases-3 (HDAC3), a member of class I HDACs, and assess the clinical significance of HDAC3 in breast cancer. Methods: Quantitative real-time polymerase chain reaction, immunohistochemistry, and western blot analysis were used to examine messenger RNA and protein expression levels. The relationships between HDAC3 expression and clinicopathological variables were analyzed. MTT assays were used to detect cell proliferation. Glucose-uptake, lactate, adenosine triphosphate, and lactate dehydrogenase assays were employed to detect aerobic glycolysis. Chromatin immunoprecipitation was used to detect microRNA-31 (miR-31) promoter binding. Results: Our data revealed that HDAC3 was upregulated in breast cancer tissue compared with matched para-carcinoma tissues, and high levels of HDAC3 were positively correlated with advanced TNM stage and N stage of cancer. Furthermore, overexpression of HDAC3 promoted breast cancer cellproliferation and aerobic glycolysis. The functional involvement of HDAC3 was related in part to the repression of miR-31 transcription via decreased histone H3 acetylation at lysine K9 levels of the miR-31 promoter. Survival analysis revealed that the level of HDAC3 was an independent prognostic factor for breast cancer patients. Conclusion: Our findings revealed that HDAC3 served as an oncogene that could promote cell proliferation and aerobic glycolysis and was predictive of a poor prognosis in breast cancer. HDAC3 participated in the cell proliferation of breast cancer, which may prove to be a pivotal epigenetic target against this devastating disease.

Inhibition of Histone Deacetylase 10 Induces Thioredoxin-Interacting Protein and Causes Accumulation of Reactive Oxygen Species in SNU-620 Human Gastric Cancer Cells

Lee, Ju-Hee,Jeong, Eun-Goo,Choi, Moon-Chang,Kim, Sung-Hak,Park, Jung-Hyun,Song, Sang-Hyun,Park, Jin-Ah,Bang, Yung-Jue,Kim, Tae-You Korean Society for Molecular and Cellular Biology 2010 Molecules and cells Vol.30 No.2

Histone deacetylase (HDAC)10, a novel class IIb histone deacetylase, is the most similar to HDAC6, since both contain a unique second catalytic domain. Unlike HDAC6, which is located in the cytoplasm, HDAC10 resides in both the nucleus and cytoplasm. The transcriptional targets of HDAC10 that are associated with HDAC10 gene regulation have not been identified. In the present study, we found that knockdown of HDAC10 significantly increased the mRNA expression levels of thioredoxin-interacting protein (TXNIP) in SNU-620 human gastric cancer cells; whereas inhibition of HDAC1, HDAC2, and HDAC6 did not affect TXNIP expression. TXNIP is the endogenous inhibitor of thioredoxin (TRX), which acts as a cellular antioxidant. Real-time PCR and immunoblot analysis confirmed that inhibition of HDAC10 induced TXNIP expression. Compared to class I only HDAC inhibitors, inhibitors targeting both class I and II upregulated TXNIP, indicating that TXNIP is regulated by class II HDACs such as HDAC10. We further verified that inhibition of HDAC10 induced release of cytochrome c and activated apoptotic signaling molecules through accumulation of reactive oxygen species (ROS). Taken together, our results demonstrate that HDAC10 is involved in transcriptional downregulation of TXNIP, leading to altered ROS signaling in human gastric cancer cells. How TXNIP is preferentially regulated by HDAC10 needs further investigation.