Sgf29 binds histone H3K4me2/3 and is required for SAGA complex recruitment and histone H3 acetylation

ABSTRACT Regulation of chromatin through histone acetylation is an important step in gene expression. The Gcn5 histone acetyltransferase is part of protein complexes, e.g., the SAGA complex, that interact with transcriptional activators, targeting the enzyme to specific promoters and assisting in recruitment of the basal RNA polymerase transcription machinery. The Ada2 protein directly binds to Gcn5 and stimulates its catalytic activity. Drosophila contains two Ada2 proteins, Drosophila Ada2a (dAda2a) and dAda2b. We have generated flies that lack dAda2b, which is part of a Drosophila SAGA-like complex. dAda2b is required for viability in Drosophila, and its deletion causes a reduction in histone H3 acetylation. A global hypoacetylation of chromatin was detected on polytene chromosomes in dAda2b mutants. This indicates that the dGcn5-dAda2b complex could have functions in addition to assisting in transcriptional activation through gene-specific acetylation. Although the Drosophila p53 protein was previously shown to interact with the SAGA-like complex in vitro, we find that p53 induction of reaper gene expression occurs normally in dAda2b mutants. Moreover, dAda2b mutant animals show excessive p53-dependent apoptosis in response to gamma radiation. Based on this result, we speculate that dAda2b may be necessary for efficient DNA repair or generation of a DNA damage signal. This could be an evolutionarily conserved function, since a yeast ada2 mutant is also sensitive to a genotoxic agent.

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Histone H3 acetylation on tRNA genes in LPS-activated macrophages

10.26226/morressier.5ebd45acffea6f735881b0a9 ◽

2020 ◽

Author(s):

Aneta Jurkiewicz

Keyword(s):

Histone H3 ◽

Trna Genes ◽

Activated Macrophages ◽

Histone H3 Acetylation ◽

H3 Acetylation

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Esculetin ameliorates insulin resistance and type 2 diabetic nephropathy through reversal of histone H3 acetylation and H2A lysine 119 monoubiquitination

Journal of Functional Foods ◽

10.1016/j.jff.2017.05.051 ◽

2017 ◽

Vol 35 ◽

pp. 256-266 ◽

Cited By ~ 6

Author(s):

Almesh Kadakol ◽

Vajir Malek ◽

Santosh Kumar Goru ◽

Anuradha Pandey ◽

Nisha Sharma ◽

...

Keyword(s):

Insulin Resistance ◽

Diabetic Nephropathy ◽

Histone H3 ◽

Histone H3 Acetylation ◽

H3 Acetylation ◽

Type 2 Diabetic

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Brd4’s Bromodomains Mediate Histone H3 Acetylation and Chromatin Remodeling in Pluripotent Cells through P300 and Brg1

Cell Reports ◽

10.1016/j.celrep.2018.10.003 ◽

2018 ◽

Vol 25 (7) ◽

pp. 1756-1771 ◽

Cited By ~ 15

Author(s):

Tao Wu ◽

Yasunao F. Kamikawa ◽

Mary E. Donohoe

Keyword(s):

Chromatin Remodeling ◽

Histone H3 ◽

Pluripotent Cells ◽

Histone H3 Acetylation ◽

H3 Acetylation

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A time-series analysis of altered histone H3 acetylation and gene expression during the course of MMAIII-induced malignant transformation of urinary bladder cells

Carcinogenesis ◽

10.1093/carcin/bgx011 ◽

2017 ◽

Vol 38 (4) ◽

pp. 378-390 ◽

Cited By ~ 4

Author(s):

Jinqiu Zhu ◽

Jie Wang ◽

Xushen Chen ◽

Maria Tsompana ◽

Daniel Gaile ◽

...

Keyword(s):

Gene Expression ◽

Time Series ◽

Urinary Bladder ◽

Time Series Analysis ◽

Malignant Transformation ◽

Histone H3 ◽

Series Analysis ◽

Histone H3 Acetylation ◽

Bladder Cells ◽

H3 Acetylation

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Butyrate Stimulates Histone H3 Acetylation, 8-Isoprostane Production, RANKL Expression, and Regulated Osteoprotegerin Expression/Secretion in MG-63 Osteoblastic Cells

International Journal of Molecular Sciences ◽

10.3390/ijms19124071 ◽

2018 ◽

Vol 19 (12) ◽

pp. 4071 ◽

Cited By ~ 11

Author(s):

Mei-Chi Chang ◽

Yunn-Jy Chen ◽

Yun-Chia Lian ◽

Bei-En Chang ◽

Chih-Chia Huang ◽

...

Keyword(s):

Protein Expression ◽

Cell Viability ◽

Butyric Acid ◽

Root Canal ◽

Histone H3 ◽

Rankl Expression ◽

Alp Activity ◽

Histone H3 Acetylation ◽

Apoptosis And Necrosis ◽

H3 Acetylation

Butyric acid as a histone deacetylase (HDAC) inhibitor is produced by a number of periodontal and root canal microorganisms (such as Porphyromonas, Fusobacterium, etc.). Butyric acid may affect the biological activities of periodontal/periapical cells such as osteoblasts, periodontal ligament cells, etc., and thus affect periodontal/periapical tissue destruction and healing. The purposes of this study were to study the toxic effects of butyrate on the matrix and mineralization marker expression in MG-63 osteoblasts. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cellular apoptosis and necrosis were analyzed by propidium iodide/annexin V flow cytometry. The protein and mRNA expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) were analyzed by Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). OPG, soluble RANKL (sRANKL), 8-isoprostane, pro-collagen I, matrix metalloproteinase-2 (MMP-2), osteonectin (SPARC), osteocalcin and osteopontin (OPN) secretion into culture medium were measured by enzyme-linked immunosorbant assay. Alkaline phosphatase (ALP) activity was checked by ALP staining. Histone H3 acetylation levels were evaluated by immunofluorescent staining (IF) and Western blot. We found that butyrate activated the histone H3 acetylation of MG-63 cells. Exposure of MG-63 cells to butyrate partly decreased cell viability with no marked increase in apoptosis and necrosis. Twenty-four hours of exposure to butyrate stimulated RANKL protein expression, whereas it inhibited OPG protein expression. Butyrate also inhibited the secretion of OPG in MG-63 cells, whereas the sRANKL level was below the detection limit. However, 3 days of exposure to butyrate (1 to 8 mM) or other HDAC inhibitors such as phenylbutyrate, valproic acid and trichostatin stimulated OPG secretion. Butyrate stimulated 8-isoprostane, MMP-2 and OPN secretion, but not procollagen I, or osteocalcin in MG-63 cells. Exposure to butyrate (2–4 mM) for 3 days markedly stimulated osteonectin secretion and ALP activity. In conclusion, higher concentrations of butyric acid generated by periodontal and root canal microorganisms may potentially induce bone destruction and impair bone repair by the alteration of OPG/RANKL expression/secretion, 8-isoprostane, MMP-2 and OPN secretion, and affect cell viability. However, lower concentrations of butyrate (1–4 mM) may stimulate ALP, osteonectin and OPG. These effects are possibly related to increased histone acetylation. These events are important in the pathogenesis and repair of periodontal and periapical destruction.

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Promoter-specific changes in initiation, elongation and homeostasis of histone H3 acetylation during CBP/p300 inhibition

eLife ◽

10.7554/elife.63512 ◽

2021 ◽

Vol 10 ◽

Author(s):

Emily Hsu ◽

Nathan R Zemke ◽

Arnold J Berk

Keyword(s):

Rna Polymerase Ii ◽

Control Point ◽

Histone H3 ◽

Airway Epithelial Cells ◽

Proximal Region ◽

Transferase Activity ◽

Transcriptional Elongation ◽

Elongation Complex ◽

Histone H3 Acetylation ◽

H3 Acetylation

Regulation of RNA Polymerase II (Pol2) elongation in the promoter proximal region is an important and ubiquitous control point for gene expression in metazoans. We report that transcription of the adenovirus 5 E4 region is regulated during the release of paused Pol2 into productive elongation by recruitment of the super elongation complex (SEC), dependent on promoter H3K18/27 acetylation by CBP/p300. We also establish that this is a general transcriptional regulatory mechanism that applies to ~6% of expressed protein-coding genes in primary human airway epithelial cells. We observed that a homeostatic mechanism maintains promoter, but not enhancer H3K18/27ac in response to extensive inhibition of CBP/p300 acetyl transferase activity by the highly specific small molecule inhibitor A-485. Further, our results suggest a function for BRD4 association at enhancers in regulating paused Pol2 release at nearby promoters. Taken together, our results uncover processes regulating transcriptional elongation by promoter region histone H3 acetylation and homeostatic maintenance of promoter, but not enhancer, H3K18/27ac in response to inhibition of CBP/p300 acetyl transferase activity.

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Interplay between Chromatin and trans-Acting Factors on the IME2 Promoter upon Induction of the Gene at the Onset of Meiosis

Molecular and Cellular Biology ◽

10.1128/mcb.01661-06 ◽

2006 ◽

Vol 27 (4) ◽

pp. 1254-1263 ◽

Cited By ~ 18

Author(s):

Tomomi Inai ◽

Masashi Yukawa ◽

Eiko Tsuchiya

Keyword(s):

Histone Deacetylase ◽

Chromatin Structure ◽

Molecular Basis ◽

Histone Acetyltransferase ◽

Histone H3 ◽

Repressive Chromatin ◽

Tata Element ◽

Histone H3 Acetylation ◽

Low Levels ◽

H3 Acetylation

ABSTRACT The IME2 gene is one of the key regulators of the initiation of meiosis in budding yeast. This gene is repressed during mitosis through the repressive chromatin structure at the promoter, which is maintained by the Rpd3-Sin3 histone deacetylase (HDAC) complex. IME2 expression in meiosis requires Gcn5/histone acetyltransferase, the transcriptional activator Ime1, and the chromatin remodeler RSC; however, the molecular basis of IME2 activation had not been previously defined. We found that, during mitotic growth, a nucleosome masked the TATA element of IME2, and this positioning depended on HDAC. This chromatin structure was remodeled at meiosis by RSC that was recruited to TATA by Ime1. Stable tethering of Ime1 to the promoter required the presence of Gcn5. Interestingly, Ime1 binding to the promoter was kept at low levels during the very early stages in meiosis, even when the levels of Ime1 and histone H3 acetylation at the promoter were at their highest, making a 4- to 6-h delay of the IME2 expression from that of IME1. HDAC was continuously present at the promoter regardless of the transcriptional condition of IME2, and deletion of RPD3 allowed the IME2 expression shortly after the expression of IME1, suggesting that HDAC plays a role in regulating the timing of IME2 expression.

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