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p53 exerts anticancer effects by regulating enhancer formation and activity

Journal of Biomedical research 2024年第4期38卷 334-347页

作者： Shuhan Chen Xuchun Wang Nan Yang Yuechi Song He Cheng Yujie Sun Key Laboratory of Human functional genomics of Jiangsu Province School of Basic Medical SciencesNanjing Medical UniversityNanjingJiangsu 211166China Department of Cell Biology School of Basic Medical SciencesNanjing Medical UniversityNanjingJiangsu 211166China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Personalized Cancer MedicineNanjing Medical UniversityNanjingJiangsu 211166China

The abnormality of the p53 tumor suppressor is crucial in lung cancer development,because p53 regulates target gene promoters to combat *** studies have shown extensive p53 binding to enhancer ***,whether p53 exerts a tumor suppressor role by shaping the enhancer landscape remains poorly *** the current study,we employed several functional genomics approaches to assess the enhancer activity at p53 binding sites throughout the genome based on our established TP53 knockout(KO)human bronchial epithelial cells(BEAS-2B).A total of 943 active regular enhancers and 370 super-enhancers(SEs)disappeared upon the deletion of p53,indicating that p53 modulates the activity of hundreds of enhancer *** found that one p53-dependent SE,located on chromosome 9 and designated as KLF4-SE,regulated the expression of the Krüppel-like factor 4(KLF4)***,the deletion of p53 significantly decreased the KLF4-SE enhancer activity and the KLF4 expression,but increased colony formation ability in the nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced cell transformation ***,in TP53 KO cells,the overexpression of KLF4 partially reversed the increased clonogenic capacity caused by p53 ***,KLF4 expression also decreased in lung cancer tissues and cell *** appeared that overexpression of KLF4 significantly suppressed the proliferation and migration of lung cancer ***,our results suggest that the regulation of enhancer formation and activity by p53 is an integral component of the p53 tumor suppressor ***,our findings offer some novel insights into the regulation mechanism of p53 in lung oncogenesis and introduce a new strategy for screening therapeutic targets.

关键词： p53 enhancer tumor malignant transformation

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BTA2 regulates tiller angle and the shoot gravity response through controlling auxin content and distribution in rice

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Journal of Integrative Plant Biology 2024年第9期66卷 1966-1982页

作者： Zhen Li Junhua Ye Qiaoling Yuan Mengchen Zhang Xingyu Wang Jing Wang Tianyi Wang Hongge Qian Xinghua Wei Yaolong Yang Lianguang Shang Yue Feng China National center for Rice Improvement State Key Laboratory of Rice Biology and BreedingChina National Rice Research InstituteHangzhou 310006China Shenzhen Branch Guangdong Laboratory of Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518124China National Nanfan research Institute(Sanya) Chinese Academy of Agricultural SciencesSanya 572024China

Tiller angle is a key agricultural trait that establishes plant architecture,which in turn strongly affects grain yield by influencing planting density in *** shoot gravity response plays a crucial role in the regulation of tiller angle in rice,but the underlying molecular mechanism is largely ***,we report the identification of the BIG TILLER ANGLE2(BTA2),which regulates tiller angle by controlling the shoot gravity response in ***-of-function mutation of BTA2 dramatically reduced auxin content and affected auxin distribution in rice shoot base,leading to impaired gravitropism and therefore a big tiller ***2 interacted with AUXIN RESPONSE FACTOR7(ARF7)to modulate rice tiller angle through the gravity signaling *** BTA2 protein was highly conserved during *** variation in the BTA2 promoter of indica cultivars harboring a less expressed BTA2 allele caused lower BTA2 expression in shoot base and thus wide tiller angle during rice *** of BTA2 significantly increased grain yield in the elite rice cultivar Huanghuazhan under appropriate dense planting *** findings thus uncovered the BTA2-ARF7 module that regulates tiller angle by mediating the shoot gravity *** work offers a target for genetic manipulation of plant architecture and valuable information for crop improvement by producing the ideal plant type.

关键词： auxin domestication gravity response rice tiller angle

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Blastoids generated purely from embryonic stem cells both in mice and humans

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Science China(Life Sciences) 2024年第2期67卷 418-420页

作者： Baojiang Wu Yanqiu Wang Jia Yan Mengya Liu Xihe Li Fuchou Tang Siqin Bao The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock Inner Mongolia UniversityHohhot 010020China research center for Animal Genetic Resources of Mongolia Plateau College of Life SciencesInner Mongolia UniversityHohhot 010020China Beijing Advanced Innovation center for genomics and Biomedical Pioneering Innovation center College of Life SciencesPeking UniversityBeijing 100871China Inner Mongolia Saikexing Institute of Breeding and Reproductive Biotechnology in Domestic Animal Hohhot 011517China

Dear Editor,Embryonic stem cells(ESCs)and trophoblast stem cells(TSCs)are derived from blastocysts(Lu et al.,2001).Blastocyst-like structures(blastoids)are self-assembled structures formed by a combination of ESCs and TSCs(Rivron et al.,2018).To increase the success rate of blastoid formation and its similarity with the features of blastocysts,some reports showed that blastoid could also be derived from a combination of three cell lines,ESCs,TSCs,and extraembryonic endoderm cells(XENs),or novel type of stem cells(Sozen et al.,2018;Weatherbee et al.,2023:Wu et al.,2023;Zhang et al.,2023;Zhang et al.,2019).

关键词： purely similarity

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Hypoxia-inducible factor-1αin myocardial infarction

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World Journal of Cardiology 2024年第4期16卷 181-185页

作者： IvanaŠkrlec Sergey N Kolomeichuk Faculty of Dental Medicine and Health Josip Juraj Strossmayer University of OsijekOsijek 31000Croatia Institute of Biology Karelia Research Center of Russian Academy of SciencesPetrozavodsk 185910Russia Laboratory for genomics Proteomicsand MetabolomicsResearch Institute of Biomedicine and Biomedical TechnologiesTyumen State Medical UniversityTyumen 625023Russia

Hypoxia-inducible factor 1(HIF1)has a crucial function in the regulation of oxygen levels in mammalian cells,especially under hypoxic *** importance in cardiovascular diseases,particularly in cardiac ischemia,is because of its ability to alleviate cardiac *** oxygen-responsive subunit,HIF1α,plays a crucial role in this process,as it has been shown to have cardioprotective effects in myocardial infarction through regulating the expression of genes affecting cellular survival,angiogenesis,and ***,HIF1αexpression induced reperfusion in the ischemic skeletal muscle,and hypoxic skin wounds in diabetic animal models showed reduced HIF1α*** expression of HIF1αhas been shown to reduce apoptosis and oxidative stress in cardiomyocytes during acute myocardial *** variations in HIF1αhave also been found to correlate with altered responses to ischemic cardiovascular *** addition,a link has been established between the circadian rhythm and hypoxic molecular signaling pathways,with HIF1αfunctioning as an oxygen sensor and circadian genes such as period circadian regulator 2 responding to changes in *** editorial analyzes the relationship between HIF1αand the circadian rhythm and highlights its significance in myocardial adaptation to *** the changes in molecular signaling pathways associated with diseases,specifically cardiovascular diseases,provides the opportunity for innovative therapeutic interventions,especially in low-oxygen environments such as myocardial infarction.

关键词： Cardiovascular pathologies Circadian genes Hypoxia-inducible factor 1 Hypoxia Gene-gene interaction

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Characterization of the molecular dysfunctions occurring in Aicardi-Goutieres syndrome patients with mutations in ADAR1

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Genes & Diseases 2024年第3期11卷 116-119页

作者： Sofan Al wardat Loredana Frasinlli Elisa Orecchini Federica Rey Silvia Anna Ciafre Silvia Galardi Jessica Garau Stella Gagliardi Simona Orcesi Davide Tonduti Stephana Carelli Cristina Cereda Ernesto Picardi Alessandro Michienzi Department of Biomedicine and Prevention University of Rome Tor VergataRome 00133Italy Pediatric Clinical research center"Romeo ed Enrica Invernizzi" Department of Biomedical and Clinical SciencesUniversity of MilanoMilano 20157Italy center of functional genomics and Rare Diseases Department of PediatricsBuzzi Children's HospitalMilano20154Italy Department of Child Neurology and Psychiatry IRccs Mondino FoundationPavia 27100Italy Unit of Pediatric Neurology C.O.A.L.A(Center for Diagnosis and Treatment of Leukodystrophies)Buzzi Children's HospitalMilano 20154Italy Department of Biosciences Biotechnologies and EnvironmentUniversityof Bari"AldoMoro"Bari 70125Italy Institute of Biomembranes Bioenergetics and Molecular Biotechnologies(IBIOM)National Research Council(CNR)Bari 70126Italy Biostructures and Biosystems National Institute(INBB) Rome00136Italy Institute of Biochemistry and Cell Biology IBBC-CNRCampus Adriano Buzzati TraversoRome 00015Italy

Aicardi-Goutieres syndrome(AGS)is a systemic inflammatory disorder caused by mutations in any one of the nine different genes,whose deficiency provokes a type I(interferon)IFN response probably central to pathogenesis.^(1) ADAR1,one of the genes mutated in AGS(AGS6),encodes for an enzyme that belongs to the ADAR family(ADAR1,ADAR2,and ADAR3)that catalyzes the conversion of adenosine to inosine within double-stranded RNAs(dsRNAs)(RNA editing A-to-1).

关键词： ADAR1 interferon res

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Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction

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Protein & Cell 2024年第1期15卷 6-20页

作者： Ning Wu Ling Wei Zhipeng Zhu Qiang Liu Kailong Li Fengbiao Mao Jie Qiao Xiaolu Zhao State Key Laboratory of Female Fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijing 100191China National Clinical research center for Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China Key Laboratory of Assisted Reproduction(Peking University) Ministry of EducationBeijing 100191China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology Beijing 100191China Institute of Medical Innovation and research Peking University Third HospitalBeijing 100191China Cancer center Peking University Third HospitalBeijing 100191China Department of Biochemistry and Biophysics Beijing Key Laboratory of Protein Posttranslational Modifications and Cell FunctionSchool of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Beijing Advanced Innovation center for genomics Beijing 100191China Peking-Tsinghua center for Life Sciences Peking UniversityBeijing 100191China

Originating but free from chromosomal DNA,extrachromosomal circular DNAs(eccDNAs)are organized in circular form and have long been found in unicellular and multicellular *** biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA,for which few detection methods are *** advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation,evolution,and drug resistance as well as aging,genomic diversity,and other biological processes,bringing it back to the research *** mechanisms of eccDNA formation have been proposed,including the breakage-fusion-bridge(BFB)and translocation-deletion-amplification *** tumors and disorders of embryonic and fetal development are major threats to human reproductive *** roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer *** present review summarized the research history,biogenesis,and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and *** also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection,prognosis,and treatment of gynecologic *** review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.

关键词： extrachromosomal circular DNAs gynecologic tumors reproduction liquid biopsy non-invasive prena-tal testing

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KoNA:Korean Nucleotide Archive as A New Data Repository for Nucleotide Sequence Data

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genomics, Proteomics & Bioinformatics 2024年第1期22卷 161-167页

作者： Gunhwan Ko Jae Ho Lee Young Mi Sim Wangho Song Byung-Ha Yoon Iksu Byeon Bang Hyuck Lee Sang-Ok Kim Jinhyuk Choi Insoo Jang Hyerin Kim Jin Ok Yang Kiwon Jang Sora Kim Jong-Hwan Kim Jongbum Jeon Jaeeun Jung Seungwoo Hwang Ji-Hwan Park Pan-Gyu Kim Seon-Young Kim Byungwook Lee Korea Bioinformation center Korea Research Institute of Bioscience&BiotechnologyDaejeon 34141Republic of Korea

During the last decade,the generation and accumulation of petabase-scale high-throughput sequencing data have resulted in great challenges,including access to human data,as well as transfer,storage,and sharing of enormous amounts of *** promote data-driven biological research,the Korean government announced that all biological data generated from government-funded research projects should be deposited at the Korea BioData Station(K-BDS),which consists of multiple databases for individual data ***,we introduce the Korean Nucleotide Archive(KoNA),a repository of nucleotide sequence *** of July 2022,the Korean Read Archive in KoNA has collected over 477 TB of raw next-generation sequencing data from national genome *** ensure data quality and prepare for international alignment,a standard operating procedure was adopted,which is similar to that of the International Nucleotide Sequence Database *** standard operating procedure includes quality control processes for submitted data and metadata using an automated pipeline,followed by manual *** ensure fast and stable data transfer,a high-speed transmission system called GBox is used in ***,the data uploaded to or downloaded from KoNA through GBox can be readily processed using a cloud computing service called *** seamless coupling of KoNA,GBox,and Bio-Express enhances the data experience,including submission,access,and analysis of raw nucleotide *** not only satisfies the unmet needs for a national sequence repository in Korea but also provides datasets to researchers globally and contributes to advances in *** KoNA is available at https://***/kona/.

关键词： Korea BioData Station Nucleotide sequence Next-generation sequencing repository genomics Deposition and access of big data

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Allelic reprogramming of chromatin states in human early embryos

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National Science Review 2024年第3期11卷 58-71页

作者： Shenli Yuan Lei Gao Wenrong Tao Jianhong Zhan Gang Lu Jingye Zhang Chuanxin Zhang Lizhi Yi Zhenbo Liu Zhenzhen Hou Min Dai Han Zhao Zi-Jiang Chen Jiang Liu Keliang Wu center for Reproductive Medicine Shandong University CAS Key Laboratory of Genome Sciences and Information Collaborative Innovation Center of Genetics and Development Beijing Institute of Genomicsand China National Center for BioinformationChinese Academy of Sciences University of Chinese Academy of Sciences CUHK-SDU Joint Laboratory on Reproductive Genetics School of Biomedical Sciences the Chinese University of Hong Kong Key Laboratory of Reproductive Endocrinology of the Ministry of Education Shandong University center for Reproductive Medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University CAS center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

The reprogramming of parental epigenomes in human early embryos remains elusive. To what extent the characteristics of parental epigenomes are conserved between humans and mice is currently unknown. Here,we mapped parental haploid epigenomes using human parthenogenetic and androgenetic embryos. Human embryos have a larger portion of genome with parentally specific epigenetic states than mouse *** allelic patterns of epigenetic states for orthologous regions are not conserved between humans and mice. Nevertheless, it is conserved that maternal DNA methylation and paternal H3K27me3 are associated with the repression of two alleles in humans and mice. In addition, for DNA-methylation-dependent imprinting, we report 19 novel imprinted genes and their associated germline differentially methylated regions. Unlike in mice, H3K27me3-dependent imprinting is not observed in human early ***, allele-specific epigenomic reprogramming is different in humans and mice.

关键词： human embryo epigenetics reprogramming DNA methylation H3K27me3 chromatin accessibility

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Lack of evidence for germline WWP1 pathogenic variants in gastrointestinal polyposis and other phenotypes suggestive of PTEN-hamartoma-tumor syndrome

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Genes & Diseases 2024年第2期11卷 524-527页

作者： Noemi Gonzalez-Abuin Tirso Pons Teresa Fuster Isabel Quintana Mariona Terradas Gemma Aiza Joan Brunet Gabriel Capellá Heather Hampel Laura Valle Hereditary Cancer Program Catalan Institute of OncologyOncobell ProgramIDIBELLHospitalet de LlobregatBarcelona 08908Spain Department of Immunology and Oncology National Center for BiotechnologySpanish National Research Council (CNB-CSIC)Madrid 28049Spain Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) Madrid 28029Spain Catalan Institute of Oncology IDIBGiGirona 17007Spain Division of Clinical Cancer genomics Department of Medical Oncology & Therapeutic ResearchCity of Hope National Cancer CenterDuarteCA 91010USA

Germline activating variants in WWP1,which encodes an E3 ubiquitin ligase that antagonizes PTEN tumor suppressive function,have been proposed as an alternative mechanism of PTEN inactivation in PTEN-hamartoma-tumor syndrome(PHTS)-like patients with wildtype PTEN.1 More specifically,heterozygous,potentially activating wwP1 variants were first identified by Lee et al in patients affected with gastrointestinal oligopolyposis,including adenomatous,hyperplastic/serrated,and hamartomatous polyps,and occasionally with colorectal cancer(Table 1).Subsequently,based on the PHTS phenotypic features,wWP1 mutational screening was performed in patients with thyroid nodules,2 or normocephalic autism spectrum disorder(ASD),3 where germline WWP1 variants were also identified(Table S1).

关键词： WWP1 gastrointestinal polyposis

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Genome editing of 30 UTR-embedded inhibitory region enables generation of gene knock-up alleles in plants

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Plant Communications 2024年第3期5卷 1-4页

作者： Hongwen Wang Dahan Zhang Mingjiang Chen Xiangbing Meng Shiwei Bai Peiyong Xin Jijun Yan Jinfang Chu Jiayang Li Hong Yu State Key Laboratory of Plant genomics and National center for Plant Gene research Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Yazhouwan National Laboratory Sanya 572024China

Dear Editor,Genome editing has revolutionized speed breeding by enabling researchers to alter the genome directly as desired(Gao,2021).The most widely used CRISPR–Cas9 technology has mainly been applied to engineer null mutations in coding sequences,with the goal of creating loss-of-function ***,upstream regulatory elements of the promoter region and 50 upstream open reading frame(uORF)have been engineered to generate gain-of-function alleles,producing versatile cis-regulatory effects,usually through changes in gene expression levels(Rodrıguez-Leal et al.,2017;Zhang et al.,2018;Song et al.,2022).

关键词： upstream breeding versatile

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