爪蟾是重要的生物医学模式动物。文章根据NCBI公布的热带爪蟾(Xenopus tropicalis)基因组数据, 利用生物信息学方法提取和鉴定了爪蟾全基因组范围的碱性螺旋-环-螺旋(bHLH)基因信息, 应用系统发生方法进行分类并做基因本体论(Gene Ontology, GO)功能富集分布分析, 以期从整体上探讨爪蟾bHLH转录因子基因家族的分类及功能。结果表明, 在热带爪蟾基因组数据库中发现了70个bHLH转录因子, 其中69个可以分别归到6大组(A~F)的34个亚家族中, 另一个为“孤儿因子”(Orphan)基因。GO富集分布统计发现有51个显著富集分布的GO注释语句, 其中转录调控活性、转录调控、DNA结合、RNA代谢过程调控、DNA依赖的转录调控、转录和转录因子活性等出现频率很高, 表明这些GO术语是爪蟾bHLH基因最常见的功能; 许多bHLH转录因子在一些重要的发育或生理过程中发挥调控作用, 如肌肉组织和器官(横纹肌、骨骼肌、眼部和咽部肌肉)的分化和发育、消化系统发育、咽部和感觉器官的发育、碱基和核苷及核酸的代谢调控、生物合成过程调控、DNA结合和蛋白质异聚化活性等。另外, 还有一些重要信号通路(Signaling pathway)的GO术语显著地富集。文章还对Hes转录因子家族做了进化分析。这些结果为热带爪蟾bHLH基因的进一步研究打下了很好的基础。
Xenopus is an important model animal for biomedicine researches. In order to probe into the classification and function of the basic helix-loop-helix (bHLH) transcription factor family, we conducted a genome-wide survey and identified 70 bHLH transcription factors using the Xenopus tropicalis genome project data in the study. Among these transcription factors, 69 bHLH transcription factors were classified into 6 large groups composed of 34 sub-families and the remaining one was classified as ‘orphan’. Results of Gene Ontology (GO) enrichment statistics showed 51 frequent GO annotation categories. Statistical analysis of the GO annotations showed that these 70 bHLH proteins tended to be fre-quently related to transcription regulator activity, regulation of transcription, DNA binding, regulation of RNA metabolic process, DNA-dependent regulation of transcription, transcription, and transcription factor activity, indicating that they were expected to be the most common GO categories of transcriptional factors. Moreover, a number of bHLH genes were revealed to play important regulation roles in special development and physiological processes, such as muscle tissue and organ (striated muscle, skeletal muscle, eye muscle, and pharyngeal muscle) differentiation and development, e.g., digestive system development, pharynx development and sensory organ development, regulation of nucleobase, nucleoside and nu-cleotide and nucleic acid metabolic process, regulation of biosynthetic process, DNA binding, and protein heterodimeriza-tion activity, etc. There were also some important signaling pathways in the significant GO categories. We made the evolu-tionary analysis of Hes transcription factor family as well. This preliminary result lays a solid foundation for further re-searches on X. tropicalis.
[1] Boggon TJ, Shan WS, Santagata S, Myers SC, Shapiro L. Implication of tubby proteins as transcription factors by structure-based functional analysis. Science, 1999, 286(5447): 2119-2125.
[2] Luscombe NM, Austin SE, Berman HM, Thornton JM. An overview of the structures of protein-DNA complexes. Genome Biol, 2000, 1(1): 1-37.
[3] Riechmann JL, Heard J, Martin G, Reuber L, Jiang CZ, Keddie J, Adam L, Pineda O, Ratcliffe OJ, Samaha RR, Creelman R, Pilgrim M, Broun P, Zhang JZ, Ghandehari D, Sherman BK, Yu GL. Arabidopsis transcription factors: genome-wide comparative analysis among eu-karyotes. Science, 2000, 290(5499): 2105-2110.
[4] Atchley WR, Fitch WM. A natural classification of the basic helix-loop-helix class of transcription factors. Proc Natl Acad Sci USA, 1997, 94(10): 5172-5176.
[5] Massari ME, Murre C. Helix-loop-helix proteins: Regulators of transcription in eucaryotic organisms. Mol Cell Biol, 2000, 20(2): 429-440.
[6] Ledent V, Vervoort M. The basic helix-loop-helix protein family: Comparative genomics and phylogenetic analysis. Genome Res, 2001, 11(5): 754-770.
[7] Stevens JD, Roalson EH, Skinner MK. Phylogenetic and expression analysis of the basic helix-loop-helix tran-scription factor gene family: genomic approach to cellular differentiation. Differentiation, 2008, 76(9): 1006-1022.
[8] Carretero-Paulet L, Galstyan A, Roig-Villanova I, Martínez-García JF, Bilbao-Castro JR, Robertson DL. Genome-Wide Classification and evolutionary analysis of the bHLH family of transcription factors in Arabidopsis, poplar, rice, moss, and algae. Plant Physiol, 2010, 153(3): 1398-1412.
[9] Murre C, McCaw PS, Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, Daughterless, MyoD and Myc proteins. Cell, 1989, 56(5): 777-783.
[10] Atchley WR, Terhalle W, Dress A. Positional dependence, cliques, and predictive motifs in the bHLH protein domain. J Mol Evol, 1999, 48(5): 501-516.
[11] Ledent V, Paquet O, Vervoort M. Phylogenetic analysis of the human basic helix-loop-helix proteins. Genome Biol, 2002, 3(6): 301-3018.
[12] Toledo-Ortiz G, Huq E, Quail PH. The Arabidopsis basic/helix-loop-helix transcription factor family. Plant Cell, 2003, 15(8): 1749-1770.
[13] Li J, Liu Q, Qiu MS, Pan YC, Li YX, Shi TL. Identification and analysis of the mouse basic/Helix-Loop-Helix transcription factor family. Biochem Biophys Res Commun, 2006, 350(3): 648-656.
[14] Simionato E, Ledent V, Richards G, Thomas-Chollier M, Kerner P, Coornaert D, Degnan BM, Vervoort M. Origin and diversification of the basic helix-loop-helix gene family in metazoans: Insights from comparative genomics. BMC Evol Biol, 2007, 7: 33.
[15] Wang Y, Chen KP, Yao Q, Wang WB, Zhu Z. The basic helix-loop-helix transcription factor family in Bombyx mori. Dev Genes Evol, 2007, 217(10): 715-723.
[16] Wang Y, Chen KP, Yao Q, Zheng XD, Yang Z. Phylogenetic analysis of zebrafish basic helix-loop-helix transcription factors. J Mol Evol, 2009, 68(6): 629-640.
[17] Liu WY, Zhao CJ. Genome-wide identification and analysis of the chicken basic helix-loop-helix factors. Comp Funct Genomics, 2010: 682095.
[18] Zheng X, Wang Y, Yao Q, Yang Z, Chen K. A genome-wide survey on basic helix-loop-helix transcription factors in rat and mouse. Mamm Genome, 2009, 20(4): 236-246.
[19] Hellsten U, Harland RM, Gilchrist MJ, Hendrix D, Jurka J, Kapitonov V, Ovcharenko I, Putnam NH, Shu SQ, Taher L, Blitz IL, Blumberg B, Dichmann DS, Dubchak I, Amaya E, Detter JC, Fletcher R, Gerhard DS, Goodstein D, Graves T, Grigoriev IV, Grimwood J, Kawashima T, Lindquist E, Lucas SM, Mead PE, Mitros T, Ogino H, Ohta Y, Poliakov AV, Pollet N, Robert J, Salamov A, Sater AK, Schmutz J, Terry A, Vize PD, Warren WC, We
