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The paternal epigenome and embryogenesis： poising mechanisms for development

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Asian Journal of Andrology 2011年第1期13卷 76-80页

作者： Timothy G Jenkins Douglas T Carrell Andrology and IVF Laboratories Department of Surgery University of Utah Salt Lake City UT 84108 USA Department of Obstetrics and Gynecology University of Utah School of Medicine Salt Lake City UT 84108 USA Department of Physiology University of Utah School of Medicine Salt Lake City UT 84108 USA

The scope of paternal contributions during early embryonic development has long been considered limited. Dramatic changes in chromatin structure throughout spermatogenesis have been thought to leave the sperm void of complex layers of epigenetic regulation over the DNA blueprint, thus leaving the balance of that regulation to the oocyte. However, recent work in the fields of epigenetics and male factor infertility has placed this long-held, and now controversial dogma, in a new light. Elegant studies investigating chromatin and epigenetic modifications in the developing sperm cell have provided new insights that may establish a more critical role for the paternal epigenome in the developing embryo. DNA methylation, histone tail modifications, targeted histone retention and protamine incorporation into the chromatin have great influence in the developing sperm cell. Perturbations in the establishment and/or maintenance of any of these epigenetic marks have been demonstrated to affect fertility status, ranging in severity from mild to catastrophic. Sperm require this myriad of chromatin structural changes not only to serve a protective role to DNA throughout spermatogenesis and future delivery to the egg, but also, it appears, to contribute to the developmental program of the future embryo. This review will focus on our current understanding of the epigenetics of sperm. We will discuss sperm-specific chromatin modifications that result in genes essential to development being poised for activation early in embryonic development, the disruption of which may result in reduced fecundity.

关键词： chromatin DNA methylation embryogenesis epigenetics histone modification male infertility

Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer

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Genomics, Proteomics & Bioinformatics 2016年第1期14卷 42-54页

作者： Yiwen Fang Melissa J. Fullwood cancer science institute of singapore national university of singapore Singapore 117599 Singapore School of Biological Sciences Nanyang Technological University Singapore 637551 Singapore Institute of Molecular and Cell Biology Agency for Science Technology and Research (A*STAR) Singapore 138673 Singapore Yale-NUS Liberal Arts College Singapore 138527 Singapore

Long non-coding RNAs （ineRNAs） play important roles in cancer. They are involved in chromatin remodeling, as well as transcriptional and post-transcriptional regulation, through a vari- ety of chromatin-based mechanisms and via cross-talk with other RNA species, lncRNAs can func- tion as decoys, scaffolds, and enhancer RNAs. This review summarizes the characteristics of lncRNAs, including their roles, functions, and working mechanisms, describes methods for identi- fying and annotating lncRNAs, and discusses future opportunities for lncRNA-based therapies using antisense oligonucleotides.

关键词： IncRNAS chromatin Transcription regulation Antisense oligonucleotides Cancer

Nuclear reprogramming: the strategy used in normal development is also used in somatic cell nuclear transfer and parthenogenesis

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Cell Research 2007年第2期17卷 135-150页

作者： Tianlong Gao~(1,*) Junke Zheng~(2,*) Fengying Xing~(2,*) Haiyan Fang~2 Feng Sun~1 Ayong Yan~2 Xun Gong~2 Hui Ding~3 Fan Tang~2 Hui Z Sheng~2 ~1Program for Graduation Studies,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China ~2Center for Developmental Biology,Xinhua Hospital,Shanghai Jiao Tong University,School of Medicine,1665 Kong Jiang Road,Shanghai 200092,China ~3School of Animal Science and Technology,Yangzhou University,Yangzhou 225009,China Program for Graduation Studies Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China Center for Developmental Biology Xinhua Hospital Shanghai Jiao Tong University School of Medicine Shanghai China School of Animal Science and Technology Yangzhou University Yangzhou China

Somatic cell nuclear transfer(SCNT)and parthenogenesis are alternative forms of reproduction and development,building new life cycles on differentiated somatic cell nuclei and duplicated maternal chromatin,*** thepreceding paper(Sun F,et al.,Cell Res 2007;17:117-134.),we showed that an"erase-and-rebuild"strategy is used innormal development to transform the maternal gene expression profile to a zygotic ***,we investigate if the samestrategy also applies to SCNT and *** relationship between chromatin and chromatin factors(CFs)during SCNT and parthenogenesis was examined using immunochemical and GFP-fusion protein *** fromthese studies indicated that soon after nuclear transfer,a majority of CFs dissociated from somatic nuclei and were re-distributed to the cytoplasm of the *** erasure process in oogenesis is recaptured during the initial phase in *** CFs entered pseudo-pronuclei shortly after their *** parthenogenesis,all parthenogenotes underwentnormal oogenesis,and thus had removed most CFs from chromosomes before the initiation of *** CFswere subsequently re-associated with female pronuclei in time and sequence similar to that in fertilized *** these data,we conclude that the"erase-and-rebuild"process observed in normal development also occurs in SCNTand in parthenogenesis,albeit in altered *** process is responsible for transcription reprogramming in ***"erase"process in SCNT is compressed and the efficiency is compromised,which likely contribute tothe developmental defects often observed in nuclear transfer(nt)***,results from this study indicatedthat the cytoplasm of an egg contains most,if not all,essential components for assembling the zygotic program and canassemble them onto appropriate diploid chromatin of distinct origins.

关键词： nuclear reprogramming SCNT parthenogenesis chromatin factors chromatin embryogenesis

Affinity of anticancer drug,daunomycin,to core histones in solution:comparison of free and cross-linked proteins

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Acta Pharmacologica Sinica 2007年第5期28卷 731-737页

作者： Azra RABBANI Sayeh ABDOSAMADI Naghmeh SARI-SARAF Institute of Biochemistry and Biophysics Department of BiochemistryUniversity of Tehran13145-1384TehranIran

Aim:The interaction of anthracycline anticancer drugs with chromatin,nucleo-somes and histone H1 has been extensively *** the present study,for thefirst time,we have investigated the binding of anthracycline antibiotic,daunomycin,to free and cross-linked thymus core histories (CL-core) in solution and in theabsence of ***:Fluorescence,UV/Vis spectroscopy and equilibriumdialysis techniques were ***:The UV spectroscopy results show thatdaunomycin induces hypochromicity in the absorption spectra of the core *** emission intensity is decreased upon daunomycin binding and theprocess is concentration *** equilibrium dialysis shows that the bind-ing is positive cooperative with the binding sites as Scatchard plot and Hill Coef-ficient confirm ***:The results suggest that daunomycin shows muchhigher affinity to core histones free in solution than to CL-core,implying that thebinding is most likely due to the accessibility of these proteins to the *** is suggested that daunomycin binds strongly to open state of histones,such asin tumor cells,rather than to their compact structure seen in normal chromatin.

关键词： anthracycline antibiotics daunomycin core histones chromatin fluorescence quenching

The oxidative DNA damage response： A review of research undertaken with Tsinghua and Xiangya students at the University of Pittsburgh

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Science China(Life Sciences) 2017年第10期60卷 1077-1080页

作者： S.Levine Luxi Sun Rong Tan Ying Gao Lu Yang Hao Chen Yaqun Teng Li Lan UPMC Hillman Cancer Center Pittsburgh PA 15213 USA Department of Microbiology and Molecular Genetics University of Pittsburgh School of Medicine Pittsburgh PA 15219 USA School of Medicine Tsinghua University Beijing 100084 China Xiangya Hospital Central South University Changsha 410008 China

Endogenous stress and exogenous toxicants(chemicals and UV light) alter genetic information either directly or indirectly through the production of reactive oxygen species(ROS), thereby driving genomic instability in cells and promoting tumorigenesis. All living cells try to faithfully preserve and transmit their genomic information from one generation to the next using DNA repair mechanisms to repair oxidative DNA damage to prevent cancer or premature aging. Oxidative DNA damage comprises a mixture of DNA lesions including base damage, DNA single strand breaks(SSBs), and DNA double strand breaks(DSBs). This review summarizes some of the studies on DNA damage response at a defined genome locus that are performed by students from the Tsinghua University School of Medicine and the School of Medicine of Central South University(Xiangya Hospital) at the University of Pittsburgh School of Medicine. A summary of their work highlights the continuous contribution of the students to a particular research program and exemplifies the achievements of this China-U.S. collaborative training program.

关键词： DNA damage chromatin telomere DNA repair

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) contributes to incorporation of histone variant H2A.Z into nucleosomes

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Protein & Cell 2019年第9期10卷 694-699页

作者： Ling-Yao Wang Yun-xiao He Min Li Jian Ding Yi Sui Joan W.Conaway Ronald C.Conaway Yong Cai Jingji Jin School of Life Sciences Jilin UniversityChangchun 130012 China Stowers Institute for Medical Research 1000E 50th StreetKansas CityMO 64110USA National Engineering Laboratory for AIDS Vaccine Jilin University Changchun 130012China Key Laboratory for Molecular Enzymology and Engineering The Ministry of EducationJilin UniversityChangchun 130012China

Current research has dem on strated that the dynamic distribution of histone variant H2A.Z at specific loci can be regulated by ATP-dependent chromatin remodelers, histone chaperones and histone post-translational mod... 详细信息

关键词： histone chromatin chaperones

Development of rabbit monoclonal and polyclonal antibodies for detection of site-specific histone modifications and their application in analyzing overall modification levels

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Cell Research 2006年第5期16卷 519-527页

作者： Lan Guo~(1,2,*) Benliang Yin~(1,*) Junli Zhou~(1,3) Xueyong Li~3 Xing Wang Deng~(1,2,3) ~1National Institute of Biological Science,Zhongguancun Life Science Park,Beijing 102206,China ~2Peking-Yale Joint Center of Plant Molecular Genetics and Agrobiotechnology,College of Life Sciences,Peking University,Beijing 100871,China ~3Department of Molecular,Cellular,and Developmental Biology,Yale University,New Haven,Connecticut 06520-8104,USA National Institute of Biological Science Zhongguancun Life Science Park Beijing China Peking-Yale Joint Center of Plant Molecular Genetics and Agrobiotechnology College of Life Sciences Peking University Beijing China Department of Molecular Cellular and Developmental Biology Yale University New Haven USA

In addition to DNA sequence information,site-specific histone modifications are another important determinant ofgene expression in a eukaryotic *** selected four modification sites in common histones that are known tosignificantly impact chromatin function and generated monoclonal or polyclonal antibodies that recognize each of thosesite-specific *** used these antibodies to demonstrate that the site-specific histone modification levelsremain relatively constant in different organs of the same *** also compared the levels of selected histonemodifications among several representative organisms and found that site-specific modifications are highly variable amongdifferent organisms,providing new insight into the evolutionary divergence of specific histone modifications.

关键词： histone modification site-specific antibody chromatin

Arabidopsis thaliana histone deacetylase1(AtHD1)is localized in euchromatic regions and demonstrates histone deacetylase activity in vitro

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Cell Research 2006年第5期16卷 479-488页

作者： Paulus M Fong Z Jeffrey Chen Department of Soil and Crop Sciences Texas A&M UniversityCollege StationTX 77843USA Molecular Cell and Developmental Biology University of Texas at AustinAustinTX78712USA

Arabidopsis thaliana histone deacetylase 1 (AtHD1 or AtHDA19),a homolog of yeast RPD3,is a global regulator ofmany physiological and developmental processes in *** spite of the genetic evidence for a role of AtHD1 in plantgene regulation and development,the biochemical and cellular properties of AtHD1 are poorly *** we reportcellular localization patterns of AtHD1 in vivo and histone deacetylase activity in *** transient and stable expres-sion of a green fluorescent protein (GFP)-tagged AtHD1 in onion cells and in roots,seeds and leaves of the transgenicArabidopsis,respectively,revealed that AtHD1 is localized in the nucleus presumably in the euchromatic regions andexcluded from the *** localization patterns of AtHD1 are different from those of AtHD2 and AtHDA6 thatare involved in nucleolus formation and silencing of transgenes and repeated DNA elements,*** addition,a histone deacetylase activity assay showed that the recombinant AtHD1 produced in bacteria demonstrated a specifichistone deacetylase activity in *** data suggest that AtHD1 is a nuclear protein and possesses histone deacetylaseactivities responsible for global transcriptional regulation important to plant growth and development.

关键词： Arabidopsis histone deacetylase RPD3 subcellular localization gene silencing chromatin

Effects of differently polarized microwave radiation on the microscopic structure of the nuclei in human fibroblasts

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2010年第10期11卷 801-805页

作者： Yuriy G.SHCKORBATOV Vladimir N.PASIUGA Elena I.GONCHARUK Tatiana Ph.PETRENKO Valentin A.GRABINA Nicolay N.KOLCHIGIN Dmitry D.IVANCHENKO Victor N.BYKOV Oleksandr M.DUMIN Kharkiv National University Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine

To investigate the influence of microwave radiation on the human fibroblast nuclei,the effects of three variants of electromagnetic wave polarization,linear and left-handed and right-handed elliptically polarized,were *** conditions were:frequency(f) 36.65 GHz,power density(P) at the surface of exposed object 1,10,30,and 100 μW/cm2,exposure time 10 *** fibroblasts growing in a monolayer on a cover slide were exposed to microwave electromagnetic *** layer of medium that covered cells during microwave exposure was about 1 mm *** were stained immediately after irradiation by 2%(w/v) orcein solution in 45%(w/v) acetic *** were made at room temperature(25 °C),and control cell samples were processed in the same *** assessed heterochromatin granule quantity(HGQ) at 600× *** irradiation at the intensity of 1 μW/cm2 produced no effect,and irradiation at the intensities of 10 and 100 μW/cm2 induced an increase in *** intense irradiation induced more chromatin *** right-handed elliptically polarized radiation revealed more biological activity than the left-handed polarized one.

关键词： Human cells chromatin Heterochromatin Electromagnetic field Elliptical polarization