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PIM1-HDAC2 axis modulates intestinal homeostasis through epigenetic modification

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3049-3067页

作者： Jianming Yang Yawen Xiao Ningning Zhao Geng Pei Yan Sun Xinyu Sun Kaiyuan Yu Chunhui Miao Ran Liu Junqiang Lv Hongyu Chu Lu Zhou Bangmao Wang Zhi Yao Quan Wang Key Laboratory of Immune Microenvironment and Disease(Ministry of Education) Tianjin Institute of ImmunologyState Key Laboratory of Experimental Hematologythe Province and Ministry Co-sponsored Collaborative Innovation Center for Medical EpigeneticsDepartment of ImmunologySchool of Basic Medical SciencesTianjin Institute of Urologythe Second Hospital of Tianjin Medical UniversityTianjin Key Laboratory of Cellular and Molecular ImmunologyTianjin Medical UniversityTianjin 300070China Department of Pathology Tianjin Medical University Cancer Institute and Hospital/National Clinical Research Center of Cancer/Key Laboratory of Cancer Prevention and TherapyTianjin/Tianjin’s Clinical Research Center of CancerTianjin 30060China Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300070China

The mucosal barrier is crucial for intestinal homeostasis,and goblet cells are essential for maintaining the mucosal barrier *** proviral integration site for Moloney murine leukemia virus-1(PIM1)kinase regulates multiple cellular functions,but its role in intestinal homeostasis during colitis is ***,we demonstrate that PIM1 is prominently elevated in the colonic epithelia of both ulcerative colitis patients and murine models,in the presence of intestinal *** PIM1 leads to decreased goblet cells,thus impairing resistance to colitis and colitis-associated colorectal cancer(CAC)in ***,PIM1 modulates goblet cell differentiation through the Wnt and Notch signaling ***,PIM1 interacts with histone deacetylase 2(HDAC2)and downregulates its level via phosphorylation,thereby altering the epigenetic profiles of Wnt signaling pathway ***,these findings investigate the unknown function of the PIM1-HDAC2 axis in goblet cell differentiation and ulcerative colitis/CAC pathogenesis,which points to the potential for PIM1-targeted therapies of ulcerative colitis and CAC.

关键词： PIM1 HDAC2 Goblet cell Gut microbiota Intestinal homeostasis epigenetic modification Ulcerative colitis CAC

Role of methionine on epigenetic modification of DNA methylation and gene expression in animals

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Animal Nutrition 2018年第1期4卷 11-16页

作者： Naifeng Zhang Feed Research Institute of Chinese Academy of Agricultural Sciences Key Laboratory of Feed Biotechnology of the Ministry of Agriculture

DNA methylation is one of the main epigenetic phenomena affecting gene *** is an important mechanism for the development of embryo,growth and health of *** a key nutritional factor limiting the synthesis of protein,methionine serves as the precursor of S-adenosylmethionine(SAM) in the hepatic one-carbon *** dietary fluctuation of methionine content can alter the levels of metabolic substrates in one-carbon metabolism,e.g.,the SAM,S-adenosylhomocysteine(SAH),and change the expression of genes related to the growth and health of animals by DNA methylation *** ratio of SAM to SAH is called ‘methylation index' but it should be carefully explained because the complexity of methylation *** of methylation in a specific cytosine-guanine(Cp G)site,rather than the whole promoter region,might be enough to change gene *** methionine cycle may provoke molecular changes of one-carbon metabolism that results in deregulation of cellular hemostasis and health *** importance of DNA methylation has been underscored but the mechanisms of methionine affecting DNA methylation are poorly *** epigenomics provides a promising insight into the targeting epigenetic changes in animals from a nutritional standpoint,which will deepen and expand our understanding of genes,molecules,tissues,and animals in which methionine alteration influences DNA methylation and gene expression.

关键词： epigenetics Methionine DNA methylation Gene expression epigenetic modification

AB035. Lactate receptor GPR81 modulates epigenetic modification in the subretina

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Annals of Eye Science 2018年第1期 441-441页

作者： Xiaojuan Yang Raphael Rouget Tang Zhu Christiane Quiniou Shasha Lv Suna Jung Francois Duhamel Houda Tahiri Samy Omri Baraa Noueihed Xin Hou JoséCarlos Rivera Mathieu Nadeau-Vallée Pierre Lachapelle Sylvain Chemtob Department of Pharmacology McGill UniversityMontréalQCCanada Department of Pharmacology Universitéde MontréalMontréalQCCanada Research Center CHU Sainte-Justine Universitéde MontréalMontréalQCCanada Department of Ophthalmology and Neurology-Neurosurgery Montréal Children’s Hospital-Research InstituteMcGill UniversityMontréalQCCanada Research Center Hôpital Maisonneuve-Rosemont Universitéde MontréalMontréalQCCanada Department of Ophthalmology Universitéde MontréalMontréalQCCanada Department of Pediatrics Universitéde MontréalMontréalQCCanada

Background:Retinal pigment epithelium(RPE)is vital for the homeostasis of the subretina including photoreceptors and ***,our previous results suggested that the recently discovered lactate receptor GPR81 is abundantly expressed in *** date,only one previous study has shown that activating GPR81 could enhance DNA repair by activating ***,we investigated whether GPR81 exhibits epigenetic modification in the subretina by using GPR81−/−***:GPR81−/−mice and wide type littermates were generated on a background of C57BL/6J *** thicknesses of their choroid were evaluated by ***,Q-PCR,western blot and choroid sprout assay were *** vitro,primary retinal pigment epithelium(pRPE)cells were isolated from mice,and cultured for ***:The thickness of choroid was reduced in GPR81−/−mice compared to GPR81+/+mice,suggesting that GPR81 is important for the integrity of *** the choroid sprout assay,lactate treated RPE/choroid complex showed a significant increase in angiogenesis compared to controls while lactate treated KO RPE/choroid complex showed no difference compared to their *** Q-PCR,most of the genes screened elevated their expression in GPR81−/−mice compared to WT mice,suggesting epigenetic modification may exist,which were confirmed by histone acetylation and HDACs activity ***:Taking together,the lactate receptor GPR81 in RPE is very important for maintaining homeostasis of the *** novel discovery sheds new light on the relationship between metabolism and epigenetic modification.

关键词： Subretina GPR81 epigenetic modification

epigenetic modifications of chronic hypoxiamediated neurodegeneration in Alzheimer’s disease

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Translational Neurodegeneration 2014年第1期3卷 40-45页

作者： Hui Liu Weidong Le Institute of Neurology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025PR China 1st Affiliated Hospital Dalian Medical UniversityDalian 116011PR China

Alzheimer’s disease(AD)is the most common neurodegenerative disorder affecting the elderly *** is characterized by progressive and gradual decline in cognitive function and memory *** familial early-onset AD is usually associated with gene mutations,the etiology of sporadic late-onset form of AD is largely *** has been reported that environmental factors and epigenetic alterations significantly contribute to the process of *** previous studies have documented that chronic hypoxia is one of the environmental factors that may trigger the AD development and aggravate the disease *** this review,we will summarize the pathological effects of chronic hypoxia on the onset and development of AD and put forward the possible molecule mechanisms underlying the chronic hypoxia mediated AD ***,we propose that epigenetic regulations may represent new opportunity for the therapeutic intervention of this disease.

关键词： Alzheimer’s disease Chronic hypoxia epigenetic modification DNA methylation Histone acetylation

Streptavidin-Biotin Complexes as Tools for Modulating an Important DNA Episgenetic modification

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Chinese Journal of Chemistry 2024年第18期42卷 2166-2172页

作者： Yongjie Liu Xinyan Xu Xingyu Liu Wei Xiong Qianqian Qi Yuanyuan Zhang Jinxuan Hou Tian Tian Xiang Zhoua Key Laboratory of Biomedical Polymers of Ministry of Education College of Chemistry and Molecular SciencesHubei Province Key Laboratory of Allergyand ImmunologyWuhan UniversityWuhanHubei 430072China Department of Thyroid&Breast Surgery Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhanHubei 430072China

DNA 5-formylcytosine(5fC)is a prominent epigenetic modification within biological *** investigations have shed light on its pivotal role in governing cell fate,gene expression,and disease ***,our comprehension of the precise control of the 5f site structure to influence its functionality remains *** this study,we have successfully achieved precise control over 5fc activity by harnessing the interaction between streptavidin and *** research underscores the potential application of interactions between biomacromolecules and small molecules in advancing the field of DNA epigenetic functional regulation.

关键词： epigenetic modification Biotin Streptavidin Selectivity Regulation

A Computational Workflow to Identify Allele-specifc Expression and epigenetic Modifcation in Maize

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Genomics, Proteomics & Bioinformatics 2013年第4期11卷 247-252页

作者： Xiaoxing Wei Xiangfeng Wang Department of Basic Medicine Medical College of Qinghai University School of Plant Sciences University of ArizonaTucson AZ 85715 USA

Allele-specific expression refers to the preferential expression of one of the two alleles in a diploid genome, which has been thought largely attributable to the associated cis-element variation and allele-specific epigenetic modification patterns. Allele-specific expression may contribute to the heterosis （or hybrid vigor） effect in hybrid plants that are produced from crosses of closely-related species, subspecies and/or inbred lines. In this study, using Illumina high-throughput sequencing of maize transcriptomics, chromatic H3K27me3 histone modification and DNA methylation data, we developed a new computational framework to identify allele-specifically expressed genes by simul- taneously tracking allele-specific gene expression patterns and the epigenetic modification landscape in the seedling tissues of hybrid maize. This approach relies on detecting nucleotide polymorphisms and any genomic structural variation between two parental genomes in order to distinguish pater- nally or maternally derived sequencing reads. This computational pipeline also incorporates a mod- ified Chi-square test to statistically identify allele-specific gene expression and epigenetic modification based on the Poisson distribution.

关键词： Allele-specific expression epigenetic modification Poisson model Hybrid maize Illumina sequencing

Optical Imaging of epigenetic modifications in Cancer:A Systematic Review

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Phenomics 2022年第2期2卷 88-101页

作者： Yang Du Pei Zhang Wei Liu Jie Tian CAS Key Laboratory of Molecular Imaging Beijing Key Laboratory of Molecular Imagingthe State Key Laboratory of Management and Control for Complex SystemsInstitute of AutomationChinese Academy of SciencesBeijing 100190China The University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Supportive Care Center and Day Oncology UnitPeking University Cancer Hospital and InstituteBeijing 100142China Beijing Advanced Innovation Center for Big Data-Based Precision Medicine School of MedicineBeihang UniversityBeijing 100191China School of Life Science and Technology Xidian UniversityXi’an 710071ShaanxiChina

Increasing evidence has demonstrated that abnormal epigenetic modifications are strongly related to cancer ***,sensitive and specific detection of epigenetic modifications could markedly improve biological investigations and cancer precision medicine.A rapid development of molecular imaging approaches for the diagnosis and prognosis of cancer has been observed during the past few *** biomarkers unique to epigenetic modifications and targeted imaging probes have been characterized and used to discriminate cancer from healthy tissues,as well as evaluate therapeutic *** this study,we summarize the latest studies associated with optical molecular imaging of epigenetic modification targets,such as those involving DNA methylation,histone modification,noncoding RNA regulation,and chromosome remodeling,and further review their clinical application on cancer diagnosis and ***,we further propose the future direc-tions for precision imaging of epigenetic modification in *** by promising clinical and preclinical studies associated with optical molecular imaging technology and epigenetic drugs,the central role of epigenetics in cancer should be increasingly recognized and accepted.

关键词： epigenetic modification Optical imaging Cancer Imaging probe

Decoding epigenetic codes: new frontiers in exploring recovery from spinal cord injury

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Neural Regeneration Research 2020年第9期15卷 1613-1622页

作者： Bo-Yin Zhang Peng-Yu Chang Qing-San Zhu Yu-Hang Zhu Saijilafu Department of Orthopedic Surgery China-Japan Union Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Radiotherapy The First Bethune Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Orthopedics The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina

Spinal cord injury that results in severe neurological disability is often *** poor clinical outcome of spinal cord injury is mainly caused by the failure to reconstruct the injured neural *** intrinsic and extrinsic determinants contribute to this inability to *** regulation acts as the driving force for multiple pathological and physiological processes in the central nervous system by modulating the expression of certain critical *** studies have demonstrated that post-SCI alteration of epigenetic landmarks is strongly associated with axon regeneration,glial activation and *** findings not only establish a theoretical foundation for further exploration of spinal cord injury,but also provide new avenues for the clinical treatment of spinal cord *** review focuses on the epigenetic regulation in axon regeneration and secondary spinal cord ***,these discoveries are a selection of epigenetic-based prognosis biomarkers and attractive therapeutic targets in the treatment of spinal cord injury.

关键词： axon regeneration epigenetic biomarkers epigenetic modification histone microRNA prognosis secondary injury spinal cord injury

Decoding the plant genome: From epigenome to 3D organization

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Journal of Genetics and Genomics 2020年第8期47卷 425-434页

作者： Weizhi Ouyang Zhilin Cao Dan Xiong Guoliang Li Xingwang Li National Key Laboratory of Crop Genetic Improvement Huazhong Agricultural UniversityWuhan430070China Department of Resources and Environment Henan University of EngineeringZhengzhou451191China Hubei Key Laboratory of Agricultural Bioinformatics and Hubei Engineering Technology Research Center of Agricultural Big Data Huazhong Agricultural UniversityWuhan430070China

The linear genome of eukaryotes is partitioned into diverse chromatin states and packaged into a threedimensional(3D)structure,which has functional implications in DNA replication,DNA repair,and transcriptional *** the past decades,research on plant functional genomics and epigenomics has made great progress,with thousands of genes cloned and molecular mechanisms of diverse biological processes ***,3D genome research has gradually attracted great attention of many plant ***,we briefly review the progress in genomic and epigenomic research in plants,with a focus on Arabidopsis and rice,and summarize the currently used technologies and advances in plant 3D genome organization *** also discuss the relationships between onedimensional linear genome sequences,epigenomic states,and the 3D chromatin *** review provides basis for future research on plant 3D genomics.

关键词： Plant genomics epigenetic modification Chromatin three-dimensional structures Genomic methods