• Title/Summary/Keyword: histone deacetylation

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Histone H4-Specific Deacetylation at Active Coding Regions by Hda1C

  • Lee, Min Kyung;Kim, TaeSoo
    • Molecules and Cells
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    • v.43 no.10
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    • pp.841-847
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    • 2020
  • Histone acetylation and deacetylation play central roles in the regulation of chromatin structure and transcription by RNA polymerase II (RNA Pol II). Although Hda1 histone deacetylase complex (Hda1C) is known to selectively deacetylate histone H3 and H2B to repress transcription, previous studies have suggested its potential roles in histone H4 deacetylation. Recently, we have shown that Hda1C has two distinct functions in histone deacetylation and transcription. Histone H4-specific deacetylation at highly transcribed genes negatively regulates RNA Pol II elongation and H3 deacetylation at inactive genes fine-tunes the kinetics of gene induction upon environmental changes. Here, we review the recent understandings of transcriptional regulation via histone deacetylation by Hda1C. In addition, we discuss the potential mechanisms for histone substrate switching by Hda1C, depending on transcriptional frequency and activity.

Fine-tuning of gene expression dynamics by the Set2-Rpd3S pathway

  • Lee, Bo Bae;Kim, Ji Hyun;Kim, TaeSoo
    • BMB Reports
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    • v.50 no.4
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    • pp.162-163
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    • 2017
  • RNA polymerase II-interacting the Set2 methyltransferase co-transcriptionally methylates histone H3 at lysine 36 within the body of genes. This modification facilitates histone deacetylation by Rpd3S HDAC in 3' transcribed regions to suppress cryptic initiation and slow elongation. Although this pathway is important for global deacetylation, no strong effects have been seen on genome-wide transcription under optimized laboratory conditions. In contrast, this pathway slows the kinetics of mRNA induction when target genes are induced upon environmental changes. Interestingly, a majority of Set2-repressed genes are overlapped by a lncRNA transcription that targets H3K36 methylation and deacetylation by Rpd3S HDAC to mRNA promoters. Furthermore, this pathway delays the induction of many cryptic transcripts upon environmental changes. Therefore, the Set2-Rpd3S HDAC pathway functions to fine-tune expression dynamics of mRNAs and ncRNAs.

A Histone Deacetylase, MoHDA1 Regulates Asexual Development and Virulence in the Rice Blast Fungus

  • Kim, Taehyun;Lee, Song Hee;Oh, Young Taek;Jeon, Junhyun
    • The Plant Pathology Journal
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    • v.36 no.4
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    • pp.314-322
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    • 2020
  • Interplay between histone acetylation and deacetylation is one of the key components in epigenetic regulation of transcription. Here we report the requirement of MoHDA1-mediated histone deacetylation during asexual development and pathogenesis for the rice blast fungus, Magnaporthe oryzae. Structural similarity and phylogenetic analysis suggested that MoHDA1 is an ortholog of Saccharomyces cerevisiae Hda1, which is a representative member of class II histone deacetylases. Targeted deletion of MoHDA1 caused a little decrease in radial growth and large reduction in asexual sporulation. Comparison of acetylation levels for H3K9 and H3K14 showed that lack of MoHDA1 gene led to significant increase in H3K9 and H3K14 acetylation level, compared to the wild-type and complementation strain, confirming that it is a bona fide histone deacetylase. Expression analysis on some of the key genes involved in asexual reproduction under sporulation-promoting condition showed almost no differences among strains, except for MoCON6 gene, which was up-regulated more than 6-fold in the mutant than wild-type. Although the deletion mutant displayed little defects in germination and subsequent appressorium formation, the mutant was compromised in its ability to cause disease. Wound-inoculation showed that the mutant is impaired in invasive growth as well. We found that the mutant was defective in appressorium-mediated penetration of host, but did not lose the ability to grow on the media containing H2O2. Taken together, our data suggest that MoHDA1-dependent histone deacetylation is important for efficient asexual development and infection of host plants in M. oryzae.

Histone Deacetylation Is Involved in Activation of CXCL10 Upon IFNγ Stimulation

  • Guo, Jin-Jun;Li, Qing-ling;Zhang, Jun;Huang, Ai-Long
    • Molecules and Cells
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    • v.22 no.2
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    • pp.163-167
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    • 2006
  • Histone deacetylase (HDAC) activity is commonly associated with transcriptional repression. However, there is also evidence for a function in transcriptional activation. Previous studies have demonstrated a fundamental role of deacetylase activity in $IFN{\alpha}$-responsive gene transcription. In the case of type II IFN ($IFN{\gamma}$) results are controversial: some genes require HDAC activity, while transcription of others is repressed by HDAC. To investigate the effect of HDAC on transcription of an $IFN{\gamma}$-activated gene, real-time PCR was used to measure CXCL10 mRNA in Hela cells stimulated with $IFN{\gamma}$ in the presence or absence of the HDAC inhibitor TSA. Chromatin imunoprecipitation combined with real-time PCR was used to check acetylation of histone H4 and recruitment of the STAT1 complex to the ISRE locus of the CXCL10 gene. Activation of CXCL10 transcription in response to $IFN{\gamma}$ was paralleled by a decrease in histone H4 acetylation and an increase in recruitment of the STAT1 complex to the CXCL10 ISRE locus. The transcription of CXCL10 and histone H4 deacetylation were blocked by TSA, but the latter had no obvious affect on recruitment of the STAT1 complex. Our data indicate that $IFN{\gamma}$ and STAT-dependent gene transcription requires the participation of HDAC, as does the $IFN{\alpha}$-STAT pathway.

Potassium Acetate Blocks Clostridium difficile Toxin A-Induced Microtubule Disassembly by Directly Inhibiting Histone Deacetylase 6, Thereby Ameliorating Inflammatory Responses in the Gut

  • Lu, Li Fang;Kim, Dae Hong;Lee, Ik Hwan;Hong, Ji;Zhang, Peng;Yoon, I Na;Hwang, Jae Sam;Kim, Ho
    • Journal of Microbiology and Biotechnology
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    • v.26 no.4
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    • pp.693-699
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    • 2016
  • Clostridium difficile toxin A is known to cause deacetylation of tubulin proteins, which blocks microtubule formation and triggers barrier dysfunction in the gut. Based on our previous finding that the Clostridium difficile toxin A-dependent activation of histone deacetylase 6 (HDAC-6) is responsible for tubulin deacetylation and subsequent microtubule disassembly, we herein examined the possible effect of potassium acetate (PA; whose acetyl group prevents the binding of tubulin to HDAC-6) as a competitive/false substrate. Our results revealed that PA inhibited toxin A-induced deacetylation of tubulin and recovered toxin A-induced microtubule disassembly. In addition, PA treatment significantly decreased the production of IL-6 (a marker of inflamed tissue) in the toxin A-induced mouse enteritis model. An in vitro HDAC assay revealed that PA directly inhibited HDAC-6-mediated tubulin deacetylation, indicating that PA acted as a false substrate for HDAC-6. These results collectively indicate that PA treatment inhibits HDAC-6, thereby reducing the cytotoxicity and inflammatory responses caused by C. difficile toxin A.

Epigenetic aspects of telomeric chromatin in Arabidopsis thaliana

  • Lee, Won Kyung;Cho, Myeon Haeng
    • BMB Reports
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    • v.52 no.3
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    • pp.175-180
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    • 2019
  • Telomeres are nucleoprotein complexes at the physical ends of linear eukaryotic chromosomes. They protect the chromosome ends from various external attacks to avoid the loss of genetic information. Telomeres are maintained by cellular activities associated with telomerase and telomere-binding proteins. In addition, epigenetic regulators have pivotal roles in controlling the chromatin state at telomeres and subtelomeric regions, contributing to the maintenance of chromosomal homeostasis in yeast, animals, and plants. Here, we review the recent findings on chromatin modifications possibly associated with the dynamic states of telomeres in Arabidopsis thaliana.

The Fission Yeast Hda1p Functions on the Regulation of Proper Cell Division

  • Hwang, Hyung-Seo;Suh, Na-Young;Song, Ki-Won
    • BMB Reports
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    • v.33 no.3
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    • pp.263-267
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    • 2000
  • We cloned $hda1^+$ (histone deacetylase 1) of fission yeast Schizosaccharomyces pombe. The hda1 of S. pombe was previously reported to encode for an active histone deacetylase (Rundlett et al., 1996; Olsson et al., 1998). The $hda1^+$ is phylogenetically related to the new open reading frame HOS2 of Saccharomyces cerevisiae and only shows a partial homology to the well-known histone deacetylase subclasses, RPD3 and HDA1. A single hda1 mRNA of 1.8 kb was detected at the same level in actively growing and nitrogen-starved cells. When highly over-expressed in S. pombe from an inducible promoter, $hda1^+$ inhibited cell proliferation and caused defects in morphology and cell division. The increased histone deacetylase activity was detected in hdar over-expressing cells. These results suggest that the Hda1p should function on the regulation of cell division possibly by (Allfrey, 1966) direct deacetylation of cytoskeletal (Wade et al., 1997) and cell division regulatory proteins, (Wolffe, 1997) or by controlling their gene expressions.

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Global Histone H4 Acetylation of IGF1 and GH Genes in Lungs of Somatic Cell Cloned Calves

  • Zhang, L.;Wang, S.H.;Fan, B.L.;Dai, Y.P.;Fei, J.;Li, N.
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.8
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    • pp.1090-1094
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    • 2006
  • Histone acetylation modification is one key mechanism in the regulation of gene activation. In this study, we investigated the global levels of histone H4 acetylation of insulin like growth factor I (IGF1) and growth hormone (GH) genes in the lungs of two somatic cell cloned calves. Data showed the levels of histone H4 acetylation of IGF1 and GH genes vary widely within different gene regions, and, in almost all regions of the two genes, acetylation levels are lower in the aberrant clone than in the normal clone. Thus we suggest that inefficient epigenetic reprogramming in the clone may affect the balance between acetylation and deacetylation, which will affect normal growth and development. These findings will also have implications for improvement of cloning success rates.

Trichostatin A, a Histone Deacetylase Inhibitor Stimulate CYP3A4 Proximal Promoter Activity in Hepa-I Cells

  • Ahn Mee Ryung;Kim Dae-Kee;Sheen Yhun Yhong
    • Archives of Pharmacal Research
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    • v.27 no.4
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    • pp.415-421
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    • 2004
  • Cytochrome P450 3A4 (CYP3A4) is the most abundant CYPs in human liver, comprising approximately $30\%$ of the total liver CYPs contents and is involved in the metabolism of more than $60\%$ of currently used therapeutic drugs. However, the molecular mechanisms underly-ing regulation of CYP3A4 gene expression have not been understood. Thus, this study has been carried out to gain the insight of the molecular mechanism of CYP3A4 gene expression, investigating if the histone deacetylation is involved in the regulation of CYP3A4 gene expression by proximal promoter. Also SXR was investigated to see if they were involved in the regulation of CYP3A4 proximal promoter activity. Hepa-1 cells were transfected with a plasmid containing ${\~}1kb$ of the human CYP3A4 proximal promoter region (863 to +64 bp) cloned in front of a reporter gene, luciferase, in the presence or absence of SXR. Transfected cells were treated with CYP3A4 inducers such as rifampicin, PCN and RU 486, in order to examine the regulation of CYP3A4 gene expression in the presence or absence of trichostatin A (TSA). In Hepa-1 cells, CYP3A4 inducers increased modestly the luciferase activity when TSA was co-treated, but this increment was not enhanced by SXR cotransfection. Taken together, these results indicated that the inhibition of histone deacetylation was required to SXR-mediated increase in CYP3A4 proximal promoter region when rifampicin, or PCN was treated. Further a trans-activation by SXR may demand other species-specific transcription factors.