Full Text:   <1827>

Summary:  <1444>

CLC number: TP181

On-line Access: 2018-01-11

Received: 2017-06-08

Revision Accepted: 2017-11-19

Crosschecked: 2017-12-15

Cited: 0

Clicked: 3403

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2018 Vol.19 No.1 P.25-37


Gene locations may contribute to predicting gene regulatory relationships

Author(s):  Jun Meng, Wen-Yuan Xu, Xiao Chen, Tao Lin, Xiao-Yu Deng

Affiliation(s):  Department of System Science and Engineering, School of Electrical Engineering, Zhejiang University, Hangzhou 310027, China; more

Corresponding email(s):   junmeng@zju.edu.cn

Key Words:  Prediction, Gene regulatory relationships, Order of gene location, Spatio-temporal neighborhood method, Zebrafish cardiogenesis

Jun Meng, Wen-Yuan Xu, Xiao Chen, Tao Lin, Xiao-Yu Deng. Gene locations may contribute to predicting gene regulatory relationships[J]. Journal of Zhejiang University Science B, 2018, 19(1): 25-37.

@article{title="Gene locations may contribute to predicting gene regulatory relationships",
author="Jun Meng, Wen-Yuan Xu, Xiao Chen, Tao Lin, Xiao-Yu Deng",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Gene locations may contribute to predicting gene regulatory relationships
%A Jun Meng
%A Wen-Yuan Xu
%A Xiao Chen
%A Tao Lin
%A Xiao-Yu Deng
%J Journal of Zhejiang University SCIENCE B
%V 19
%N 1
%P 25-37
%@ 1673-1581
%D 2018
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1700303

T1 - Gene locations may contribute to predicting gene regulatory relationships
A1 - Jun Meng
A1 - Wen-Yuan Xu
A1 - Xiao Chen
A1 - Tao Lin
A1 - Xiao-Yu Deng
J0 - Journal of Zhejiang University Science B
VL - 19
IS - 1
SP - 25
EP - 37
%@ 1673-1581
Y1 - 2018
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1700303

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.




Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Akazawa H, Komuro I, 2003. Roles of cardiac transcription factors in cardiac hypertrophy. Circ Res, 92(10):1079-1088.

[2]Alexander J, Stainier DYR, 1999. A molecular pathway leading to endoderm formation in zebrafish. Curr Biol, 9(20):1147-1157.

[3]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.

[4]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.

[5]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.

[6]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.

[7]Bishopric NH, 2005. Evolution of the heart from bacteria to man. Ann NY Acad Sci, 1047(1):13-29.

[8]Cai X, Hagedorn CH, Cullen BR, 2004. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA, 10(12):1957-1966.

[9]Chiavacci E, Dolfi L, Verduci L, et al., 2012. MicroRNA 218 mediates the effects of Tbx5a over-expression on zebrafish heart development. PLoS ONE, 7(11):e50536.

[10]Chen K, Rajewsky N, 2007. The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet, 8(2):93-103.

[11]Chen W, Huang J, Yu X, et al., 2015. Identification of microRNAs and their target genes in Alport syndrome using deep sequencing of iPSCs samples. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 16(3):235-250.

[12]Esquela-Kerscher A, Slack FJ, 2006. Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer, 6(4):259-269.

[13]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.

[14]Glickman NS, Yelon D, 2002. Cardiac development in zebrafish: coordination of form and function. Semin Cell Dev Biol, 13(6):507-513.

[15]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.

[16]Huttenhower C, Haley EM, Hibbs MA, et al., 2009. Exploring the human genome with functional maps. Genome Res, 19(6):1093-1106.

[17]Kikuchi K, Holdway JE, Werdich AA, et al., 2010. Primary contribution to zebrafish heart regeneration by gata4+ cardiomyocytes. Nature, 464(7288):601-605.

[18]Kloosterman WP, Steiner FA, Berezikov E, et al., 2006. Cloning and expression of new microRNAs from zebrafish. Nucleic Acids Res, 34(9):2558-2569.

[19]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.

[20]Lee I, Li Z, Marcotte EM, 2007. An improved, bias-reduced probabilistic functional gene network of baker’s yeast, Saccharomyces cerevisiae. PLoS ONE, 2(10):e988.

[21]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.

[22]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.

[23]Lee Y, Kim M, Han J, et al., 2004. MicroRNA genes are transcribed by RNA polymerase II. EMBO J, 23(20):4051-4060.

[24]Lim LP, Lau NC, Garrett-Engele P, et al., 2005. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature, 433(7027):769-773.

[25]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).

[26]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.

[27]Ma S, Gong Q, Bohnert HJ, 2007. An Arabidopsis gene network based on the graphical Gaussian model. Genome Res, 17(11):1614-1625.

[28]Moorman AFM, Christoffels VM, 2003. Cardiac chamber formation: development, genes, and evolution. Physiol Rev, 83(4):1223-1267.

[29]Morton SU, Scherz PJ, Cordes KR, et al., 2008. microRNA-138 modulates cardiac patterning during embryonic development. Proc Natl Acad Sci USA, 105(46):17830-17835.

[30]Moulton J, 2010. The miR-143-adducin3 pathway is essential for cardiac chamber morphogenesis. Development, 137(11):1887-1896.

[31]Nemer M, 2008. Genetic insights into normal and abnormal heart development. Cardiovasc Pathol, 17(1):48-54.

[32]Okamura K, Hagen JW, Duan H, et al., 2007. The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell, 130(1):89-100.

[33]Olson EN, 2006. Gene regulatory networks in the evolution and development of the heart. Science, 313(5795):1922-1927.

[34]Plageman TF, Yutzey KE, 2004. Differential expression and function of Tbx5 and Tbx20 in cardiac development. J Biol Chem, 279(18):19026-19034.

[35]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.

[36]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.

[37]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.

[38]Romer AS, 1967. Major steps in vertebrate evolution. Science, 158(3809):1629-1637.

[39]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.

[40]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.

[41]Serbedzija GN, Chen JN, Fishman MC, 1998. Regulation in the heart field of zebrafish. Development, 125(6):1095-1101.

[42]Simões-Costa MS, Vasconcelos M, Sampaio AC, et al., 2005. The evolutionary origin of cardiac chambers. Dev Biol, 277(1):1-15.

[43]Stainier DYR, 2001. Zebrafish genetics and vertebrate heart formation. Nat Rev Genet, 2(1):39-48.

[44]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.

[45]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.

[46]Yelon D, Ticho B, Halpern ME, et al., 2000. The bHLH transcription factor Hand2 plays parallel roles in zebrafish heart and pectoral fin development. Development, 127(12):2573-2582.

[47]Ying SY, Lin SL, 2006. Current perspectives in intronic microRNAs (miRNAs). J Biomed Sci, 13(1):5-15.

[48]Zeng L, Carter AD, Childs SJ, 2009. miR-145 directs intestinal maturation in zebrafish. Proc Natl Acad Sci USA, 106(42):17793-17798.

[49]Zhang LF, Gui YH, Wang YX, et al., 2010. Effect of Tbx1 knock down on cardiac performance in zebrafish. Chin Med J, 123(9):1182-1189.

[50]Zhong W, Sternberg PW, 2006. Genome-wide prediction of C. elegans genetic interactions. Science, 311(3766):1481-1484.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE