基因位置可以用于预测基因调控关系（英文）
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摘要
目的:证明基因位置顺序与基因调控顺序的关系,说明利用基因位置顺序信息可以作为预测基因调控关系的先验知识。创新点:通过研究与斑马鱼心脏发育阶段有关的基因和mi RNA,利用时空邻域法,建立了一个基于时间的基因调控网络。通过这个基因调控网络,我们获得了一些特殊的基因调控通路和基因之间调控的时间顺序。通过研究斑马鱼心脏发育阶段有关的基因在染色体上的位置,将基因位置顺序与基因调控时间顺序比较,我们发现了这两个顺序具有逆转现象。这个逆转现象的存在,可以帮助我们利用基因位置顺序来预测基因调控关系和调控的时间顺序。方法:采用时空邻域法研究了斑马鱼心脏发育阶段的基因和mi RNA,建立基因调控网络(图5),并通过进一步比较,得到了基因位置顺序和基因调控时间顺序的联系。结论:基因位置顺序信息可以用于预测基因调控关系。
We propose that locations of genes on chromosomes can contribute to the prediction of gene regulatory relationships. We constructed a time-based gene regulatory network of zebrafish cardiogenesis on the basis of a spatio-temporal neighborhood method. Through the network, specific regulatory pathways and order of gene expression during zebrafish cardiogenesis were obtained. By comparing the order with locations of these genes on chromosomes, we discovered that there exists a reversal phenomenon between the order and order of gene locations. The discovery provides an inherent rule to instruct exploration of gene regulatory relationships. Specifically, the discovery can help to predict if regulatory relationships between genes exist and contribute to evaluating the correctness of discovered gene regulatory relationships.
We propose that locations of genes on chromosomes can contribute to the prediction of gene regulatory relationships. We constructed a time-based gene regulatory network of zebrafish cardiogenesis on the basis of a spatio-temporal neighborhood method. Through the network, specific regulatory pathways and order of gene expression during zebrafish cardiogenesis were obtained. By comparing the order with locations of these genes on chromosomes, we discovered that there exists a reversal phenomenon between the order and order of gene locations. The discovery provides an inherent rule to instruct exploration of gene regulatory relationships. Specifically, the discovery can help to predict if regulatory relationships between genes exist and contribute to evaluating the correctness of discovered gene regulatory relationships.
引文
Akazawa H,Komuro I,2003.Roles of cardiac transcription factors in cardiac hypertrophy.Circ Res,92(10):1079-1088.https://doi.org/10.1161/01.RES.0000072977.86706.23
Alexander J,Stainier DYR,1999.A molecular pathway leading to endoderm formation in zebrafish.Curr Biol,9(20):1147-1157.https://doi.org/10.1016/S0960-9822(00)80016-0
Anchel D,Ching RW,Cotton R,et al.,2016.A novel single cell method to identify the genetic composition at a single nuclear body.Sci Rep,6:29191.https://doi.org/10.1038/srep29191
Ataliotis P,Ivins S,Mohun TJ,et al.,2005.XTbx1 is a transcriptional activator involved in head and pharyngeal arch development in Xenopus laevis.Dev Dyn,232(4):979-991.https://doi.org/10.1002/dvdy.20276
Bassel GW,Glaab E,Marquez J,et al.,2011.Functional network construction in Arabidopsis using rule-based machine learning on large-scale data sets.Plant Cell,23(9):3101-3116.https://doi.org/10.1105/tpc.111.088153
Benson DW,Silberbach GM,Kavanaughmchugh A,et al.,1999.Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways.J Clin Invest,104(11):1567-1573.https://doi.org/10.1172/JCI8154
Bishopric NH,2005.Evolution of the heart from bacteria to man.Ann NY Acad Sci,1047(1):13-29.https://doi.org/10.1196/annals.1341.002
Cai X,Hagedorn CH,Cullen BR,2004.Human micro RNAs are processed from capped,polyadenylated transcripts that can also function as m RNAs.RNA,10(12):1957-1966.https://doi.org/10.1261/rna.7135204
Chiavacci E,Dolfi L,Verduci L,et al.,2012.Micro RNA 218mediates the effects of Tbx5a over-expression on zebrafish heart development.PLo S ONE,7(11):e50536.https://doi.org/10.1371/journal.pone.0050536
Chen K,Rajewsky N,2007.The evolution of gene regulation by transcription factors and micro RNAs.Nat Rev Genet,8(2):93-103.https://doi.org/10.1038/nrg1990
Chen W,Huang J,Yu X,et al.,2015.Identification of micro RNAs and their target genes in Alport syndrome using deep sequencing of i PSCs samples.J Zhejiang Univ-Sci B(Biomed&Biotechnol),16(3):235-250.https://doi.org/10.1631/jzus.B1400272
Esquela-Kerscher A,Slack FJ,2006.Oncomirs-micro RNAs with a role in cancer.Nat Rev Cancer,6(4):259-269.https://doi.org/10.1038/nrc1840
Ghosh TK,Song FF,Packham EA,et al.,2009.Physical interaction between TBX5 and MEF2C is required for early heart development.Mol Cell Biol,29(8):2205-2218.https://doi.org/10.1128/MCB.01923-08
Glickman NS,Yelon D,2002.Cardiac development in zebrafish:coordination of form and function.Semin Cell Dev Biol,13(6):507-513.https://doi.org/10.1016/S1084952102001040
Harrelson Z,Kelly RG,Goldin SN,et al.,2004.Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development.Development,131(20):5041-5052.https://doi.org/10.1242/dev.01378
Huttenhower C,Haley EM,Hibbs MA,et al.,2009.Exploring the human genome with functional maps.Genome Res,19(6):1093-1106.https://doi.org/10.1101/gr.082214.108
Kikuchi K,Holdway JE,Werdich AA,et al.,2010.Primary contribution to zebrafish heart regeneration by gata4+cardiomyocytes.Nature,464(7288):601-605.https://doi.org/10.1038/nature08804
Kloosterman WP,Steiner FA,Berezikov E,et al.,2006.Cloning and expression of new micro RNAs from zebrafish.Nucleic Acids Res,34(9):2558-2569.https://doi.org/10.1093/nar/gkl278
Kourmpetis YA,van Dijk AD,van Ham RC,et al.,2011.Genome-wide computational function prediction of Arabidopsis proteins by integration of multiple data sources.Plant Physiol,155(1):271-281.https://doi.org/10.1104/pp.110.162164
Lee I,Li Z,Marcotte EM,2007.An improved,bias-reduced probabilistic functional gene network of baker’s yeast,Saccharomyces cerevisiae.PLo S ONE,2(10):e988.https://doi.org/10.1371/journal.pone.0000988
Lee I,Lehner B,Crombie C,et al.,2008.A single gene network accurately predicts phenotypic effects of gene perturbation in Caenorhabditis elegans.Nat Genet,40(2):181-188.https://doi.org/10.1038/ng.2007.70
Lee I,Ambaru B,Thakkar P,et al.,2010.Rational association of genes with traits using a genome-scale gene network for Arabidopsis thaliana.Nat Biotechnol,28(2):149-156.https://doi.org/10.1038/nbt.1603
Lee Y,Kim M,Han J,et al.,2004.Micro RNA genes are transcribed by RNA polymerase II.EMBO J,23(20):4051-4060.https://doi.org/10.1038/sj.emboj.7600385
Lim LP,Lau NC,Garrett-Engele P,et al.,2005.Microarray analysis shows that some micro RNAs downregulate large numbers of target m RNAs.Nature,433(7027):769-773.https://doi.org/10.1038/nature03315
Liu D,Wang YX,HU JY,et al.,2008.The effects of connexin43 down regulation on the development of the embryonic heart and vasculature in zebrafish.Prog Biochem Biophys,35(7):766-771(in Chinese).
Ma L,Ma L,Schwartz RJ,et al.,2005.Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning.Development,132(24):5601-5611.https://doi.org/10.1242/dev.02156
Ma S,Gong Q,Bohnert HJ,2007.An Arabidopsis gene network based on the graphical Gaussian model.Genome Res,17(11):1614-1625.https://doi.org/10.1101/gr.6911207
Moorman AFM,Christoffels VM,2003.Cardiac chamber formation:development,genes,and evolution.Physiol Rev,83(4):1223-1267.https://doi.org/10.1152/physrev.00006.2003
Morton SU,Scherz PJ,Cordes KR,et al.,2008.micro RNA-138 modulates cardiac patterning during embryonic development.Proc Natl Acad Sci USA,105(46):17830-17835.https://doi.org/10.1073/pnas.0804673105
Moulton J,2010.The mi R-143-adducin3 pathway is essential for cardiac chamber morphogenesis.Development,137(11):1887-1896.https://doi.org/10.1242/dev.050526
Nemer M,2008.Genetic insights into normal and abnormal heart development.Cardiovasc Pathol,17(1):48-54.https://doi.org/10.1016/j.carpath.2007.06.005
Okamura K,Hagen JW,Duan H,et al.,2007.The mirtron pathway generates micro RNA-class regulatory RNAs in Drosophila.Cell,130(1):89-100.https://doi.org/10.1016/j.cell.2007.06.028
Olson EN,2006.Gene regulatory networks in the evolution and development of the heart.Science,313(5795):1922-1927.https://doi.org/10.1126/science.1132292
Plageman TF,Yutzey KE,2004.Differential expression and function of Tbx5 and Tbx20 in cardiac development.JBiol Chem,279(18):19026-19034.https://doi.org/10.1074/jbc.M314041200
Prall OWJ,Menon MK,Solloway MJ,et al.,2007.An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation.Cell,128(5):947-959.https://doi.org/10.1016/j.cell.2007.01.042
Qu X,Jia H,Garrity DM,et al.,2008.Ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish.Dev Biol,317(2):486-496.https://doi.org/10.1016/j.ydbio.2008.02.044
Reifers F,Walsh EC,Léger S,et al.,2000.Induction and differentiation of the zebrafish heart requires fibroblast growth factor 8(fgf8/acerebellar).Development,127(2):225-235.
Romer AS,1967.Major steps in vertebrate evolution.Science,158(3809):1629-1637.https://doi.org/10.1126/science.158.3809.1629
Schlange T,Andrée B,Arnold HH,et al.,2000.BMP2 is required for early heart development during a distinct time period.Mech Dev,91(1-2):259-270.https://doi.org/10.1016/S0925-4773(99)00311-1
Schultheiss TM,Burch JB,Lassar AB,1997.A role for bone morphogenetic proteins in the induction of cardiac myogenesis.Genes Dev,11(4):451-462.https://doi.org/10.1101/gad.11.4.451
Serbedzija GN,Chen JN,Fishman MC,1998.Regulation in the heart field of zebrafish.Development,125(6):1095-1101.
Sim?es-Costa MS,Vasconcelos M,Sampaio AC,et al.,2005.The evolutionary origin of cardiac chambers.Dev Biol,277(1):1-15.https://doi.org/10.1016/j.ydbio.2004.09.026
Stainier DYR,2001.Zebrafish genetics and vertebrate heart formation.Nat Rev Genet,2(1):39-48.https://doi.org/10.1038/35047564
Stennard FA,Costa MW,Elliott DA,et al.,2003.Cardiac T-box factor Tbx20 directly interacts with Nkx2-5,GATA4,and GATA5 in regulation of gene expression in the developing heart.Dev Biol,262(2):206-224.https://doi.org/10.1016/S0012-1606(03)00385-3
Yelon D,Horne SA,Stainier DYR,1999.Restricted expression of cardiac myosin genes reveals regulated aspects of heart tube assembly in zebrafish.Dev Biol,214(1):23-37.https://doi.org/10.1006/dbio.1999.9406
Yelon D,Ticho B,Halpern ME,et al.,2000.The b HLH transcription factor Hand2 plays parallel roles in zebrafish heart and pectoral fin development.Development,127(12):2573-2582.
Ying SY,Lin SL,2006.Current perspectives in intronic micro RNAs(mi RNAs).J Biomed Sci,13(1):5-15.https://doi.org/10.1007/s11373-005-9036-8
Zeng L,Carter AD,Childs SJ,2009.mi R-145 directs intestinal maturation in zebrafish.Proc Natl Acad Sci USA,106(42):17793-17798.https://doi.org/10.1073/pnas.0903693106
Zhang LF,Gui YH,Wang YX,et al.,2010.Effect of Tbx1knock down on cardiac performance in zebrafish.Chin Med J,123(9):1182-1189.https://doi.org/10.3760/cma.j.issn.0366-6999.2010.09.015
Zhong W,Sternberg PW,2006.Genome-wide prediction of C.elegans genetic interactions.Science,311(3766):1481-1484.https://doi.org/10.1126/science.1123287
Alexander J,Stainier DYR,1999.A molecular pathway leading to endoderm formation in zebrafish.Curr Biol,9(20):1147-1157.https://doi.org/10.1016/S0960-9822(00)80016-0
Anchel D,Ching RW,Cotton R,et al.,2016.A novel single cell method to identify the genetic composition at a single nuclear body.Sci Rep,6:29191.https://doi.org/10.1038/srep29191
Ataliotis P,Ivins S,Mohun TJ,et al.,2005.XTbx1 is a transcriptional activator involved in head and pharyngeal arch development in Xenopus laevis.Dev Dyn,232(4):979-991.https://doi.org/10.1002/dvdy.20276
Bassel GW,Glaab E,Marquez J,et al.,2011.Functional network construction in Arabidopsis using rule-based machine learning on large-scale data sets.Plant Cell,23(9):3101-3116.https://doi.org/10.1105/tpc.111.088153
Benson DW,Silberbach GM,Kavanaughmchugh A,et al.,1999.Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways.J Clin Invest,104(11):1567-1573.https://doi.org/10.1172/JCI8154
Bishopric NH,2005.Evolution of the heart from bacteria to man.Ann NY Acad Sci,1047(1):13-29.https://doi.org/10.1196/annals.1341.002
Cai X,Hagedorn CH,Cullen BR,2004.Human micro RNAs are processed from capped,polyadenylated transcripts that can also function as m RNAs.RNA,10(12):1957-1966.https://doi.org/10.1261/rna.7135204
Chiavacci E,Dolfi L,Verduci L,et al.,2012.Micro RNA 218mediates the effects of Tbx5a over-expression on zebrafish heart development.PLo S ONE,7(11):e50536.https://doi.org/10.1371/journal.pone.0050536
Chen K,Rajewsky N,2007.The evolution of gene regulation by transcription factors and micro RNAs.Nat Rev Genet,8(2):93-103.https://doi.org/10.1038/nrg1990
Chen W,Huang J,Yu X,et al.,2015.Identification of micro RNAs and their target genes in Alport syndrome using deep sequencing of i PSCs samples.J Zhejiang Univ-Sci B(Biomed&Biotechnol),16(3):235-250.https://doi.org/10.1631/jzus.B1400272
Esquela-Kerscher A,Slack FJ,2006.Oncomirs-micro RNAs with a role in cancer.Nat Rev Cancer,6(4):259-269.https://doi.org/10.1038/nrc1840
Ghosh TK,Song FF,Packham EA,et al.,2009.Physical interaction between TBX5 and MEF2C is required for early heart development.Mol Cell Biol,29(8):2205-2218.https://doi.org/10.1128/MCB.01923-08
Glickman NS,Yelon D,2002.Cardiac development in zebrafish:coordination of form and function.Semin Cell Dev Biol,13(6):507-513.https://doi.org/10.1016/S1084952102001040
Harrelson Z,Kelly RG,Goldin SN,et al.,2004.Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development.Development,131(20):5041-5052.https://doi.org/10.1242/dev.01378
Huttenhower C,Haley EM,Hibbs MA,et al.,2009.Exploring the human genome with functional maps.Genome Res,19(6):1093-1106.https://doi.org/10.1101/gr.082214.108
Kikuchi K,Holdway JE,Werdich AA,et al.,2010.Primary contribution to zebrafish heart regeneration by gata4+cardiomyocytes.Nature,464(7288):601-605.https://doi.org/10.1038/nature08804
Kloosterman WP,Steiner FA,Berezikov E,et al.,2006.Cloning and expression of new micro RNAs from zebrafish.Nucleic Acids Res,34(9):2558-2569.https://doi.org/10.1093/nar/gkl278
Kourmpetis YA,van Dijk AD,van Ham RC,et al.,2011.Genome-wide computational function prediction of Arabidopsis proteins by integration of multiple data sources.Plant Physiol,155(1):271-281.https://doi.org/10.1104/pp.110.162164
Lee I,Li Z,Marcotte EM,2007.An improved,bias-reduced probabilistic functional gene network of baker’s yeast,Saccharomyces cerevisiae.PLo S ONE,2(10):e988.https://doi.org/10.1371/journal.pone.0000988
Lee I,Lehner B,Crombie C,et al.,2008.A single gene network accurately predicts phenotypic effects of gene perturbation in Caenorhabditis elegans.Nat Genet,40(2):181-188.https://doi.org/10.1038/ng.2007.70
Lee I,Ambaru B,Thakkar P,et al.,2010.Rational association of genes with traits using a genome-scale gene network for Arabidopsis thaliana.Nat Biotechnol,28(2):149-156.https://doi.org/10.1038/nbt.1603
Lee Y,Kim M,Han J,et al.,2004.Micro RNA genes are transcribed by RNA polymerase II.EMBO J,23(20):4051-4060.https://doi.org/10.1038/sj.emboj.7600385
Lim LP,Lau NC,Garrett-Engele P,et al.,2005.Microarray analysis shows that some micro RNAs downregulate large numbers of target m RNAs.Nature,433(7027):769-773.https://doi.org/10.1038/nature03315
Liu D,Wang YX,HU JY,et al.,2008.The effects of connexin43 down regulation on the development of the embryonic heart and vasculature in zebrafish.Prog Biochem Biophys,35(7):766-771(in Chinese).
Ma L,Ma L,Schwartz RJ,et al.,2005.Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning.Development,132(24):5601-5611.https://doi.org/10.1242/dev.02156
Ma S,Gong Q,Bohnert HJ,2007.An Arabidopsis gene network based on the graphical Gaussian model.Genome Res,17(11):1614-1625.https://doi.org/10.1101/gr.6911207
Moorman AFM,Christoffels VM,2003.Cardiac chamber formation:development,genes,and evolution.Physiol Rev,83(4):1223-1267.https://doi.org/10.1152/physrev.00006.2003
Morton SU,Scherz PJ,Cordes KR,et al.,2008.micro RNA-138 modulates cardiac patterning during embryonic development.Proc Natl Acad Sci USA,105(46):17830-17835.https://doi.org/10.1073/pnas.0804673105
Moulton J,2010.The mi R-143-adducin3 pathway is essential for cardiac chamber morphogenesis.Development,137(11):1887-1896.https://doi.org/10.1242/dev.050526
Nemer M,2008.Genetic insights into normal and abnormal heart development.Cardiovasc Pathol,17(1):48-54.https://doi.org/10.1016/j.carpath.2007.06.005
Okamura K,Hagen JW,Duan H,et al.,2007.The mirtron pathway generates micro RNA-class regulatory RNAs in Drosophila.Cell,130(1):89-100.https://doi.org/10.1016/j.cell.2007.06.028
Olson EN,2006.Gene regulatory networks in the evolution and development of the heart.Science,313(5795):1922-1927.https://doi.org/10.1126/science.1132292
Plageman TF,Yutzey KE,2004.Differential expression and function of Tbx5 and Tbx20 in cardiac development.JBiol Chem,279(18):19026-19034.https://doi.org/10.1074/jbc.M314041200
Prall OWJ,Menon MK,Solloway MJ,et al.,2007.An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation.Cell,128(5):947-959.https://doi.org/10.1016/j.cell.2007.01.042
Qu X,Jia H,Garrity DM,et al.,2008.Ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish.Dev Biol,317(2):486-496.https://doi.org/10.1016/j.ydbio.2008.02.044
Reifers F,Walsh EC,Léger S,et al.,2000.Induction and differentiation of the zebrafish heart requires fibroblast growth factor 8(fgf8/acerebellar).Development,127(2):225-235.
Romer AS,1967.Major steps in vertebrate evolution.Science,158(3809):1629-1637.https://doi.org/10.1126/science.158.3809.1629
Schlange T,Andrée B,Arnold HH,et al.,2000.BMP2 is required for early heart development during a distinct time period.Mech Dev,91(1-2):259-270.https://doi.org/10.1016/S0925-4773(99)00311-1
Schultheiss TM,Burch JB,Lassar AB,1997.A role for bone morphogenetic proteins in the induction of cardiac myogenesis.Genes Dev,11(4):451-462.https://doi.org/10.1101/gad.11.4.451
Serbedzija GN,Chen JN,Fishman MC,1998.Regulation in the heart field of zebrafish.Development,125(6):1095-1101.
Sim?es-Costa MS,Vasconcelos M,Sampaio AC,et al.,2005.The evolutionary origin of cardiac chambers.Dev Biol,277(1):1-15.https://doi.org/10.1016/j.ydbio.2004.09.026
Stainier DYR,2001.Zebrafish genetics and vertebrate heart formation.Nat Rev Genet,2(1):39-48.https://doi.org/10.1038/35047564
Stennard FA,Costa MW,Elliott DA,et al.,2003.Cardiac T-box factor Tbx20 directly interacts with Nkx2-5,GATA4,and GATA5 in regulation of gene expression in the developing heart.Dev Biol,262(2):206-224.https://doi.org/10.1016/S0012-1606(03)00385-3
Yelon D,Horne SA,Stainier DYR,1999.Restricted expression of cardiac myosin genes reveals regulated aspects of heart tube assembly in zebrafish.Dev Biol,214(1):23-37.https://doi.org/10.1006/dbio.1999.9406
Yelon D,Ticho B,Halpern ME,et al.,2000.The b HLH transcription factor Hand2 plays parallel roles in zebrafish heart and pectoral fin development.Development,127(12):2573-2582.
Ying SY,Lin SL,2006.Current perspectives in intronic micro RNAs(mi RNAs).J Biomed Sci,13(1):5-15.https://doi.org/10.1007/s11373-005-9036-8
Zeng L,Carter AD,Childs SJ,2009.mi R-145 directs intestinal maturation in zebrafish.Proc Natl Acad Sci USA,106(42):17793-17798.https://doi.org/10.1073/pnas.0903693106
Zhang LF,Gui YH,Wang YX,et al.,2010.Effect of Tbx1knock down on cardiac performance in zebrafish.Chin Med J,123(9):1182-1189.https://doi.org/10.3760/cma.j.issn.0366-6999.2010.09.015
Zhong W,Sternberg PW,2006.Genome-wide prediction of C.elegans genetic interactions.Science,311(3766):1481-1484.https://doi.org/10.1126/science.1123287