keyword
https://read.qxmd.com/read/38448574/guiding-the-hbo1-complex-function-through-the-jade-subunit
#21
JOURNAL ARTICLE
Nitika Gaurav, Akinori Kanai, Catherine Lachance, Khan L Cox, Jiuyang Liu, Adrian T Grzybowski, Nehmé Saksouk, Brianna J Klein, Yosuke Komata, Shuhei Asada, Alexander J Ruthenburg, Michael G Poirier, Jacques Côté, Akihiko Yokoyama, Tatiana G Kutateladze
JADE is a core subunit of the HBO1 acetyltransferase complex that regulates developmental and epigenetic programs and promotes gene transcription. Here we describe the mechanism by which JADE facilitates recruitment of the HBO1 complex to chromatin and mediates its enzymatic activity. Structural, genomic and complex assembly in vivo studies show that the PZP (PHD1-zinc-knuckle-PHD2) domain of JADE engages the nucleosome through binding to histone H3 and DNA and is necessary for the association with chromatin targets...
March 6, 2024: Nature Structural & Molecular Biology
https://read.qxmd.com/read/38446667/mof-mediated-acetylation-of-uhrf1-enhances-uhrf1-e3-ligase-activity-to-facilitate-dna-methylation-maintenance
#22
JOURNAL ARTICLE
Linsheng Wang, Xi Yang, Kaiqiang Zhao, Shengshuo Huang, Yiming Qin, Zixin Chen, Xiaobin Hu, Guoxiang Jin, Zhongjun Zhou
The multi-domain protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) recruits DNMT1 for DNA methylation maintenance during DNA replication. Here, we show that MOF (males absent on the first) acetylates UHRF1 at K670 in the pre-RING linker region, whereas HDAC1 deacetylates UHRF1 at the same site. We also identify that K667 and K668 can also be acetylated by MOF when K670 is mutated. The MOF/HDAC1-mediated acetylation in UHRF1 is cell-cycle regulated and peaks at G1/S phase, in line with the function of UHRF1 in recruiting DNMT1 to maintain DNA methylation...
March 5, 2024: Cell Reports
https://read.qxmd.com/read/38446206/ing4-and-ing5-are-essential-for-histone-h3-lysine-14-acetylation-and-epicardial-cell-lineage-development
#23
JOURNAL ARTICLE
Sophia Y Y Mah, Hannah K Vanyai, Connie S N Li-Wai-Suen, Alexandra L Garnham, Jessica Wynn, Maria I Bergamasco, Shezlie Malelang, Stephen Wilcox, Christine Biben, Gordon K Smyth, Tim Thomas, Anne K Voss
Inhibitor of growth 4 and 5 (ING4, ING5) are structurally similar chromatin-binding proteins in the KAT6A, KAT6B and KAT7 histone acetyltransferase protein complexes. Heterozygous mutations in the KAT6A or KAT6B gene cause human disorders with cardiac defects, but the contribution of their chromatin-adaptor proteins to development is unknown. We found that Ing5-/- mice had isolated cardiac ventricular septal defects. Ing4-/-Ing5-/- embryos failed to undergo chorioallantoic fusion and arrested in development at embryonic day 8...
March 1, 2024: Development
https://read.qxmd.com/read/38439957/epc1-2-regulate-hematopoietic-stem-and-progenitor-cell-proliferation-by-modulating-h3-acetylation-and-dlst
#24
JOURNAL ARTICLE
WenYe Liu, Xi Liu, LingYa Li, ZhiPeng Tai, GuoLiang Li, Jing-Xia Liu
Enhancers of polycomb 1 (EPC1) and 2 (EPC2) are involved in multiple biological processes as components of histone acetyltransferases/deacetylase complexes and transcriptional cofactors, and their dysfunction was associated with developmental defects and diseases. However, it remains unknown how their dysfunction induces hematopoietic stem and progenitor cell (HSPC) defects. Here, we show that depletion of EPC1 / 2 significantly reduced the number of hematopoietic stem and progenitor cells (HSPCs) in the aorta-gonad mesonephros and caudal hematopoietic tissue regions by impairing HSPC proliferation, and consistently downregulated the expression of HSPC genes in K562 cells...
March 15, 2024: IScience
https://read.qxmd.com/read/38421638/hbo1-determines-smad-action-in-pluripotency-and-mesendoderm-specification
#25
JOURNAL ARTICLE
Cong Zhang, Yongli Shan, Huaisong Lin, Yanqi Zhang, Qi Xing, Jinmin Zhu, Tiancheng Zhou, Aiping Lin, Qianyu Chen, Junwei Wang, Guangjin Pan
TGF-β signaling family plays an essential role to regulate fate decisions in pluripotency and lineage specification. How the action of TGF-β family signaling is intrinsically executed remains not fully elucidated. Here, we show that HBO1, a MYST histone acetyltransferase (HAT) is an essential cell intrinsic determinant for TGF-β signaling in human embryonic stem cells (hESCs). HBO1-/- hESCs fail to response to TGF-β signaling to maintain pluripotency and spontaneously differentiate into neuroectoderm...
February 29, 2024: Nucleic Acids Research
https://read.qxmd.com/read/38417480/histone-h3k4ac-as-a-marker-of-active-transcription-start-sites-and-enhancers-plays-roles-in-histone-eviction-and-rna-transcription
#26
JOURNAL ARTICLE
Jin Kang, Yujin Kang, AeRi Kim
The lysine 4 of histone H3 (H3K4) can be methylated or acetylated into four states: H3K4me1, H3K4me2, H3K4me3, or H3K4ac. Unlike H3K4 methylation, the genome-wide distribution and functional roles of H3K4ac remain unclear. To understand the relationship of acetylation with methylation at H3K4 and to explore the roles of H3K4ac in the context of chromatin, we analyzed H3K4ac across the human genome and compared it with H3K4 methylation in K562 cells. H3K4ac was positively correlated with H3K4me1/2/3 in reciprocal analysis...
February 26, 2024: Biochimica et Biophysica Acta. Gene Regulatory Mechanisms
https://read.qxmd.com/read/38417317/mechanism-of-kat2a-regulation-of-h3k36ac-in-manganese-induced-oxidative-damage-to-mitochondria-in-the-nervous-system-and-intervention-by-curcumin
#27
JOURNAL ARTICLE
Yan Liu, Jia-Min Zeng, Hua Zhao, Chun-Yan Ao, Li-Hong Ao, Jia-Qi Ban, Jun Li
Excessive exposure to manganese in the environment or workplace is strongly linked to neurodegeneration and cognitive impairment, but the precise pathogenic mechanism and preventive measures are still not fully understood. The study aimed to investigate manganese -induced oxidative damage in the nervous system from an epigenetic perspective, focusing on the H3K36ac-dependent antioxidant pathway. Additionally, it sought to examine the potential of curcumin in preventing manganese-induced oxidative damage. Histopathology and transmission electron microscopy revealed that apoptosis and necrosis of neurons and mitochondrial ultrastructure damage were observed in the striatum of manganese-exposed rats...
February 27, 2024: Ecotoxicology and Environmental Safety
https://read.qxmd.com/read/38416273/involvement-of-histone-acetyltransferase-1-hat1-in-the-spermatogenesis-of-non-condensed-nuclear-sperm-in-chinese-mitten-crab-eriocheir-sinensis
#28
JOURNAL ARTICLE
Huiting Liu, Yulian Tang, Lishuang Sun, Shu Li, Lvjing Luo, Zhengyu Chen, Genliang Li
Chinese mitten crab, Eriocheir sinensis, is a decapod crustacean with a special, non-condensated nucleus in the sperm. Studies have shown that the nuclear compact state of male germ cells during the spermatogenesis is closely related to histone modification. To explore the possible role of histone acetyltransferase 1 (HAT1) in the chromatin organization during the E. sinensis spermatogenesis, we took the testis tissues of both adult and juvenile crabs as the materials of study and analyzed the biological functions of HAT1 by whole transcriptome sequencing and bioinformatics, then further analyzed the expression and distribution of HAT1 using the methods of RT-qRCR, western blotting, and immunofluorescence location...
February 28, 2024: Biochemical Genetics
https://read.qxmd.com/read/38411274/kat8-sirt7-mediated-fascin-k41-acetylation-deacetylation-regulates-tumor-metastasis-in-esophageal-squamous-cell-carcinoma
#29
JOURNAL ARTICLE
Da-Jia Li, Yin-Wei Cheng, Jin-Mei Pan, Zhen-Chang Guo, Shao-Hong Wang, Qing-Feng Huang, Ping-Juan Nie, Wen-Qi Shi, Xiu-E Xu, Bing Wen, Jin-Ling Zhong, Zhi-Da Zhang, Zhi-Yong Wu, Hui Zhao, Lian-Di Liao, Jian-Yi Wu, Kai Zhang, Geng Dong, En-Min Li, Li-Yan Xu
Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia...
February 27, 2024: Journal of Pathology
https://read.qxmd.com/read/38410425/the-mitochondrial-thiolase-acat1-regulates-monocyte-macrophage-type-i-interferon-via-epigenetic-control
#30
Jing Wu, Komudi Singh, Vivian Shing, Anand K Gupta, Rebecca D Huffstutler, Duck-Yeon Lee, Michael N Sack
Lipid-derived acetyl-CoA is shown to be the major carbon source for histone acetylation. However, there is no direct evidence demonstrating lipid metabolic pathway contribututions to this process. Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) catalyzes the final step of ß-oxidation, the aerobic process catabolizing fatty acids (FA) into acetyl-CoA. To investigate this in the context of immunometabolism, we generated macrophage cell line lacking ACAT1. 13 C-carbon tracing combined with mass spectrometry confirmed incorporation of FA-derived carbons into histone H3 and this incorporation was reduced in ACAT1 KO macrophage cells...
January 31, 2024: bioRxiv
https://read.qxmd.com/read/38408879/hdac-inhibitors-as-pharmacological-treatment-for-duchenne-muscular-dystrophy-a-discovery-journey-from-bench-to-patients
#31
REVIEW
Chiara Mozzetta, Vittorio Sartorelli, Christian Steinkuhler, Pier Lorenzo Puri
Earlier evidence that targeting the balance between histone acetyltransferases (HATs) and deacetylases (HDACs), through exposure to HDAC inhibitors (HDACis), could enhance skeletal myogenesis, prompted interest in using HDACis to promote muscle regeneration. Further identification of constitutive HDAC activation in dystrophin-deficient muscles, caused by dysregulated nitric oxide (NO) signaling, provided the rationale for HDACi-based therapeutic interventions for Duchenne muscular dystrophy (DMD). In this review, we describe the molecular, preclinical, and clinical evidence supporting the efficacy of HDACis in countering disease progression by targeting pathogenic networks of gene expression in multiple muscle-resident cell types of patients with DMD...
February 25, 2024: Trends in Molecular Medicine
https://read.qxmd.com/read/38407474/processivity-and-specificity-of-histone-acetylation-by-the-male-specific%C3%A2-lethal-complex
#32
JOURNAL ARTICLE
Anna E Kiss, Anuroop V Venkatasubramani, Dilan Pathirana, Silke Krause, Aline Campos Sparr, Jan Hasenauer, Axel Imhof, Marisa Müller, Peter B Becker
Acetylation of lysine 16 of histone H4 (H4K16ac) stands out among the histone modifications, because it decompacts the chromatin fiber. The metazoan acetyltransferase MOF (KAT8) regulates transcription through H4K16 acetylation. Antibody-based studies had yielded inconclusive results about the selectivity of MOF to acetylate the H4 N-terminus. We used targeted mass spectrometry to examine the activity of MOF in the male-specific lethal core (4-MSL) complex on nucleosome array substrates. This complex is part of the Dosage Compensation Complex (DCC) that activates X-chromosomal genes in male Drosophila...
February 26, 2024: Nucleic Acids Research
https://read.qxmd.com/read/38407438/the-jet-like-chromatin-structure-defines-active-secondary-metabolism-in-fungi
#33
JOURNAL ARTICLE
Wenyong Shao, Jingrui Wang, Yueqi Zhang, Chaofan Zhang, Jie Chen, Yun Chen, Zhangjun Fei, Zhonghua Ma, Xuepeng Sun, Chen Jiao
Eukaryotic genomes are spatially organized within the nucleus in a nonrandom manner. However, fungal genome arrangement and its function in development and adaptation remain largely unexplored. Here, we show that the high-order chromosome structure of Fusarium graminearum is sculpted by both H3K27me3 modification and ancient genome rearrangements. Active secondary metabolic gene clusters form a structure resembling chromatin jets. We demonstrate that these jet-like domains, which can propagate symmetrically for 54 kb, are prevalent in the genome and correlate with active gene transcription and histone acetylation...
February 26, 2024: Nucleic Acids Research
https://read.qxmd.com/read/38397020/anserine-a-histidine-containing-dipeptide-suppresses-pressure-overload-induced-systolic-dysfunction-by-inhibiting-histone-acetyltransferase-activity-of-p300-in-mice
#34
JOURNAL ARTICLE
Yoichi Sunagawa, Ryosuke Tsukabe, Yudai Irokawa, Masafumi Funamoto, Yuto Suzuki, Miho Yamada, Satoshi Shimizu, Yasufumi Katanasaka, Toshihide Hamabe-Horiike, Yuto Kawase, Ryuya Naruta, Kana Shimizu, Kiyoshi Mori, Ryota Hosomi, Maki Komiyama, Koji Hasegawa, Tatsuya Morimoto
Anserine, an imidazole dipeptide, is present in the muscles of birds and fish and has various bioactivities, such as anti-inflammatory and anti-fatigue effects. However, the effect of anserine on the development of heart failure remains unknown. We cultured primary cardiomyocytes with 0.03 mM to 10 mM anserine and stimulated them with phenylephrine for 48 h. Anserine significantly suppressed the phenylephrine-induced increases in cardiomyocyte hypertrophy, ANF and BNP mRNA levels, and histone H3K9 acetylation...
February 16, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38386554/histone-deacetylase-oshda706-orchestrates-rice-broad-spectrum-antiviral-immunity-and-is-impeded-by-a-viral-effector
#35
JOURNAL ARTICLE
Zihang Yang, Juan Du, Xiaoxiang Tan, Hehong Zhang, Lulu Li, Yanjun Li, Zhongyan Wei, Zhongtian Xu, Yuwen Lu, Jianping Chen, Zongtao Sun
Lysine acetylation is a dynamic post-translational modification of proteins. Extensive studies have revealed that the acetylation modulated by histone acetyltransferases and histone deacetylases (HDACs) plays a crucial role in regulating protein function. However, there has been limited focus on how HDACs regulate jasmonic acid (JA) biosynthesis in plants. Here, we uncover that the protein stability of OsLOX14, a critical enzyme involved in JA biosynthesis, is regulated by a histone deacetylase, OsHDA706, and is hindered by a viral protein...
February 21, 2024: Cell Reports
https://read.qxmd.com/read/38383863/hyperacetylated-histone-h4-is-a-source-of-carbon-contributing-to-lipid-synthesis
#36
JOURNAL ARTICLE
Evelina Charidemou, Roberta Noberini, Chiara Ghirardi, Polymnia Georgiou, Panayiota Marcou, Andria Theophanous, Katerina Strati, Hector Keun, Volker Behrends, Tiziana Bonaldi, Antonis Kirmizis
Histone modifications commonly integrate environmental cues with cellular metabolic outputs by affecting gene expression. However, chromatin modifications such as acetylation do not always correlate with transcription, pointing towards an alternative role of histone modifications in cellular metabolism. Using an approach that integrates mass spectrometry-based histone modification mapping and metabolomics with stable isotope tracers, we demonstrate that elevated lipids in acetyltransferase-depleted hepatocytes result from carbon atoms derived from deacetylation of hyperacetylated histone H4 flowing towards fatty acids...
February 21, 2024: EMBO Journal
https://read.qxmd.com/read/38383216/histone-lysine-acetyltransferase-inhibitors-an-emerging-class-of-drugs-for-cancer-therapy
#37
REVIEW
Jeffrey White, Frederick A Derheimer, Kristen Jensen-Pergakes, Shawn O'Connell, Shikhar Sharma, Noah Spiegel, Thomas A Paul
Lysine acetyltransferases (KATs) are a family of epigenetic enzymes involved in the regulation of gene expression; they represent a promising class of emerging drug targets. The frequent molecular dysregulation of these enzymes, as well as their mechanistic links to biological functions that are crucial to cancer, have led to exploration around the development of small-molecule inhibitors against KATs. Despite early challenges, recent advances have led to the development of potent and selective enzymatic and bromodomain (BRD) KAT inhibitors...
February 20, 2024: Trends in Pharmacological Sciences
https://read.qxmd.com/read/38382924/imd2-which-is-located-near-the-boundary-of-heterochromatin-regions-is-regulated-by-the-use-of-multiple-hat-related-factors
#38
JOURNAL ARTICLE
Takahito Ayano, Masaya Oki
In Saccharomyces cerevisiae, boundaries formed by DNA sequence-dependent or -independent histone modifications stop the spread of the heterochromatin region formed via the Sir complex. However, it is unclear whether the histone modifiers that control DNA sequence-independent boundaries function in a chromosome-specific or -nonspecific manner. In this study, we evaluated the effects of the SAGA complex, a histone acetyltransferase (HAT) complex, and its relationship with other histone-modifying enzymes to clarify the mechanism underlying boundary regulation of the IMD2 gene on the right subtelomere of chromosome VIII...
February 21, 2024: Genes & Genetic Systems
https://read.qxmd.com/read/38376217/the-c-terminal-protein-interaction-domain-of-the-chromatin-reader-yaf9-is-critical-for-pathogenesis-of-candida-albicans
#39
JOURNAL ARTICLE
Tricia L Lo, Qi Wang, Joshua Nickson, Bryce J W van Denderen, Deanna Deveson Lucas, Her Xiang Chai, Gavin J Knott, Harshini Weerasinghe, Ana Traven
Fungal infections cause a large health burden but are treated by only a handful of antifungal drug classes. Chromatin factors have emerged as possible targets for new antifungals. These targets include the reader proteins, which interact with posttranslationally modified histones to influence DNA transcription and repair. The YEATS domain is one such reader recognizing both crotonylated and acetylated histones. Here, we performed a detailed structure/function analysis of the Candida albicans YEATS domain reader Yaf9, a subunit of the NuA4 histone acetyltransferase and the SWR1 chromatin remodeling complex...
February 20, 2024: MSphere
https://read.qxmd.com/read/38354231/biphasic-regulation-of-epigenetic-state-by-matrix-stiffness-during-cell-reprogramming
#40
JOURNAL ARTICLE
Yang Song, Jennifer Soto, Sze Yue Wong, Yifan Wu, Tyler Hoffman, Navied Akhtar, Sam Norris, Julia Chu, Hyungju Park, Douglas O Kelkhoff, Cheen Euong Ang, Marius Wernig, Andrea Kasko, Timothy L Downing, Mu-Ming Poo, Song Li
We investigate how matrix stiffness regulates chromatin reorganization and cell reprogramming and find that matrix stiffness acts as a biphasic regulator of epigenetic state and fibroblast-to-neuron conversion efficiency, maximized at an intermediate stiffness of 20 kPa. ATAC sequencing analysis shows the same trend of chromatin accessibility to neuronal genes at these stiffness levels. Concurrently, we observe peak levels of histone acetylation and histone acetyltransferase (HAT) activity in the nucleus on 20 kPa matrices, and inhibiting HAT activity abolishes matrix stiffness effects...
February 16, 2024: Science Advances
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