脊椎动物基因组中转录因子结合位点的分布差异比较
|
摘要
目的探索4种脊椎动物转录因子结合位点(TFBS)在基因组分布情况。方法使用Bowtie比对软件将4个物种高通量测序数据进行序列比对,获得染色质开放区间,基于Cis-BP数据库的转录因子模体(motif),采用FIMO算法识别染色质开放区间上TFBS区域,对TFBS在基因组的分布情况、序列特征、是否存在聚集情况进行分析。结果编码基因启动子上下游区域处于开放状态的基因数目比例不同;相同TFBS在4个物种中的识别位点数目不同; 4种脊椎动物TFBS在基因组分布位置相似,主要分布于基因间区、内含子区,少量分布于编码蛋白区、启动子区; 4个物种的TFBS在基因组均呈现聚集分布,聚集区间长度不同,担尼鱼(斑马鱼)、黑猩猩的聚集区间长度> 2000 bp,小鼠聚集区间长度约500 bp,人的聚集区间长度约650 bp。结论 4种脊椎动物的TFBS在基因组分布大部分保守,聚集区间长度存在差别。
Objective To explore the distribution of transcription factor binding sites( TFBSs) among genomes of four vertebrates[Danio rerio( zebrafish),Mus musculus( mouse),Pans troglodytes( chimpanzee),and Homo sapiens( human) ].Methods The location of TFBSs,used in the analysis,was identified in the open chromatin using the FIMO algorithm by searching the Cis-BP database. Based on these regions,the distribution of TFBSs,sequence features and TFBSs cluster regions were developed. Results The rate at which TFBSs differences were accumulated among these four vertebrates by comparing the distribution in the genomes was assessed. The proportion of genes in the promoter regions was different. More TFBSs were distributed in the intergenic region and intron than in the coding sequence and promoter. The TFBSs of these four vertebrates were distributed in clusters in the genomes. The distance of the TFBSs cluster region was more than 2000 bp in zebrafish and chimpanzees,about 500 bp in mice,and about 650 bp in humans. Conclusion The distribution of the majority of TFBSs is conserved among genomes of four vertebrates.
Objective To explore the distribution of transcription factor binding sites( TFBSs) among genomes of four vertebrates[Danio rerio( zebrafish),Mus musculus( mouse),Pans troglodytes( chimpanzee),and Homo sapiens( human) ].Methods The location of TFBSs,used in the analysis,was identified in the open chromatin using the FIMO algorithm by searching the Cis-BP database. Based on these regions,the distribution of TFBSs,sequence features and TFBSs cluster regions were developed. Results The rate at which TFBSs differences were accumulated among these four vertebrates by comparing the distribution in the genomes was assessed. The proportion of genes in the promoter regions was different. More TFBSs were distributed in the intergenic region and intron than in the coding sequence and promoter. The TFBSs of these four vertebrates were distributed in clusters in the genomes. The distance of the TFBSs cluster region was more than 2000 bp in zebrafish and chimpanzees,about 500 bp in mice,and about 650 bp in humans. Conclusion The distribution of the majority of TFBSs is conserved among genomes of four vertebrates.
引文
[1] King MC,Wilson AC. Evolution at two levels in humans andchimpanzees[J]. Science,1975,188(4184):107-116.
[2] Tuˇgrul M,Paixo T,Barton NH,et al. Dynamics of transcrip-tion factor binding site evolution[J]. PLo S Genet,2015,11(11):e1005639.
[3] Ho JW,Jung YL,Liu T,et al. Comparative analysis of metazoanchromatin organization[J]. Nature,2014,512(7515):449-452.
[4] Villar D,Flicek P,Odom DT. Evolution of transcription factorbinding in metazoans-mechanisms and functional implications[J]. Nat Rev Genet,2014,15(4):221-233.
[5] Ludwig MZ,Bergman C,Patel NH,et al. Evidence for stabili-zing selection in a eukaryotic enhancer element[J]. Nature,2000,403(6769):564.
[6] He Q,Bardet AF,Patton B,et al. High conservation of transcrip-tion factor binding and evidence for combinatorial regulationacross six Drosophila species[J]. Nat Genet,2011,43(5):414-420.
[7] Molloy PL. Electrophoretic mobility shift assays[J]. MethodsMol Biol,2000,130(19):235-246.
[8] Brenowitz M,Senear DF,Shea MA,et al. Quantitative DNasefootprint titration:a method for studying protein-DNA interactions[J]. Methods Enzymol,1986,130(4):132-181.
[9] Andrews S,Fast QC. A Quality Control Tool for High Through-put SequenceData[EB/OL]. http://www. bioinformatics. babra-ham. ac. uk?/projects/fastqc/. 2010.
[10] Langmead B,Salzberg SL. Fast gapped-read alignment with Bowtie2[J]. Nat Methods,2012,9(4):357-359.
[11] Li H,Handsaker B,Wysoker A,et al. The sequence alignment/map(SAM)format and SAMtools[J]. Bioinformatics,2009,25(1 Pt 2):1653-1654.
[12] Quinlan AR,Hall IM. BEDTools:a flexible suite of utilities forcomparing genomic features[J]. Bioinformatics,2010,26(6):841.
[13] Zhang Y,Liu T,Meyer CA,et al. Model-based analysis of ChIP-Seq(MACS)[J]. Genome Biol,2008,9(9):R137.
[14] Matys V,Fricke E,Geffers R,et al. TRANSFAC:transcrip-tional regulation,from patterns to profiles[J]. Nucleic AcidsRes,2003,31(1):374-378.
[15] Sandelin A,Alkema W,Engstrm P,et al. JASPAR:an open-access database for eukaryotic transcription factor binding profiles[J]. Nucleic Acids Res,2004,32(Suppl 1):D91-D94.
[16] Weirauch M,Yang A,Albu M,et al. Determination and infer-ence of eukaryotic transcription factor sequence specificity[J].Cell,2014,158(6):1431-1443.
[17] Bussemaker HJ,Li H,Siggia ED. Building a dictionary for ge-nomes:identification of presumptive regulatory sites by statisticalanalysis[J]. Proc Natl Acad Sci USA,2000,97(18):10096-10100.
[18] Sinha S,Tompa M. Discovery of novel transcription factor bindingsites by statistical overrepresentation[J]. Nucleic Acids Res,2003,31(13):3586-3588.
[19] Bailey TL,Elkan C. Unsupervised learning of multiple motifs inbiopolymers using expectation maximization[J]. Mach Learn,1995,21(1-2):51-80.
[20] Hertz GZ,Stormo GD. Identifying DNA and protein patterns withstatistically significant alignments of multiple sequences[J].Bioinformatics,1999,15(8):563-577.
[21] Aleksandrushkina NI,Egorova LA. Nucleotide makeup of theDNA of thermophilic bacteria of the genus Thermus[J]. Mikrobi-ologiia,1978,47(2):250-252.
[22] Bailey TL,Boden M,Buske FA,et al. MEME Suite:tools formotif discovery and searching[J]. Nucleic Acids Res,2009,37(Web Server issue):W202-W208.
[23] Bhattacharyya N,Banerjee D. Transcriptional regulatory se-quences within the first intron of the chicken apolipoproteinAI(apoAI)gene[J]. Gene,1999,234(2):371.
[24] Gerstein MB,Lu ZJ,Van Nostrand EL,et al. Integrative analysisof the Caenorhabditis elegans genome by the modENCODE project[J]. Science,2010,330(6012):1775-1787.
[25] Moorman C,Sun LV,Wang J,et al. Hotspots of transcriptionfactor colocalization in the genome of Drosophila melanogaster[J]. Proc Natl Acad Sci USA,2006,103(32):12027-12032.
[26] Nègre N,Brown CD,Ma L,et al. A cis-regulatory map of theDrosophila genome[J]. Nature,2011,471(7339):527-531.
[27] Yan J,Enge M,Whitington T,et al. Transcription factor bindingin human cells occurs in dense clusters formed around cohesinanchor sites[J]. Cell,2013,154(4):801-813.
[2] Tuˇgrul M,Paixo T,Barton NH,et al. Dynamics of transcrip-tion factor binding site evolution[J]. PLo S Genet,2015,11(11):e1005639.
[3] Ho JW,Jung YL,Liu T,et al. Comparative analysis of metazoanchromatin organization[J]. Nature,2014,512(7515):449-452.
[4] Villar D,Flicek P,Odom DT. Evolution of transcription factorbinding in metazoans-mechanisms and functional implications[J]. Nat Rev Genet,2014,15(4):221-233.
[5] Ludwig MZ,Bergman C,Patel NH,et al. Evidence for stabili-zing selection in a eukaryotic enhancer element[J]. Nature,2000,403(6769):564.
[6] He Q,Bardet AF,Patton B,et al. High conservation of transcrip-tion factor binding and evidence for combinatorial regulationacross six Drosophila species[J]. Nat Genet,2011,43(5):414-420.
[7] Molloy PL. Electrophoretic mobility shift assays[J]. MethodsMol Biol,2000,130(19):235-246.
[8] Brenowitz M,Senear DF,Shea MA,et al. Quantitative DNasefootprint titration:a method for studying protein-DNA interactions[J]. Methods Enzymol,1986,130(4):132-181.
[9] Andrews S,Fast QC. A Quality Control Tool for High Through-put SequenceData[EB/OL]. http://www. bioinformatics. babra-ham. ac. uk?/projects/fastqc/. 2010.
[10] Langmead B,Salzberg SL. Fast gapped-read alignment with Bowtie2[J]. Nat Methods,2012,9(4):357-359.
[11] Li H,Handsaker B,Wysoker A,et al. The sequence alignment/map(SAM)format and SAMtools[J]. Bioinformatics,2009,25(1 Pt 2):1653-1654.
[12] Quinlan AR,Hall IM. BEDTools:a flexible suite of utilities forcomparing genomic features[J]. Bioinformatics,2010,26(6):841.
[13] Zhang Y,Liu T,Meyer CA,et al. Model-based analysis of ChIP-Seq(MACS)[J]. Genome Biol,2008,9(9):R137.
[14] Matys V,Fricke E,Geffers R,et al. TRANSFAC:transcrip-tional regulation,from patterns to profiles[J]. Nucleic AcidsRes,2003,31(1):374-378.
[15] Sandelin A,Alkema W,Engstrm P,et al. JASPAR:an open-access database for eukaryotic transcription factor binding profiles[J]. Nucleic Acids Res,2004,32(Suppl 1):D91-D94.
[16] Weirauch M,Yang A,Albu M,et al. Determination and infer-ence of eukaryotic transcription factor sequence specificity[J].Cell,2014,158(6):1431-1443.
[17] Bussemaker HJ,Li H,Siggia ED. Building a dictionary for ge-nomes:identification of presumptive regulatory sites by statisticalanalysis[J]. Proc Natl Acad Sci USA,2000,97(18):10096-10100.
[18] Sinha S,Tompa M. Discovery of novel transcription factor bindingsites by statistical overrepresentation[J]. Nucleic Acids Res,2003,31(13):3586-3588.
[19] Bailey TL,Elkan C. Unsupervised learning of multiple motifs inbiopolymers using expectation maximization[J]. Mach Learn,1995,21(1-2):51-80.
[20] Hertz GZ,Stormo GD. Identifying DNA and protein patterns withstatistically significant alignments of multiple sequences[J].Bioinformatics,1999,15(8):563-577.
[21] Aleksandrushkina NI,Egorova LA. Nucleotide makeup of theDNA of thermophilic bacteria of the genus Thermus[J]. Mikrobi-ologiia,1978,47(2):250-252.
[22] Bailey TL,Boden M,Buske FA,et al. MEME Suite:tools formotif discovery and searching[J]. Nucleic Acids Res,2009,37(Web Server issue):W202-W208.
[23] Bhattacharyya N,Banerjee D. Transcriptional regulatory se-quences within the first intron of the chicken apolipoproteinAI(apoAI)gene[J]. Gene,1999,234(2):371.
[24] Gerstein MB,Lu ZJ,Van Nostrand EL,et al. Integrative analysisof the Caenorhabditis elegans genome by the modENCODE project[J]. Science,2010,330(6012):1775-1787.
[25] Moorman C,Sun LV,Wang J,et al. Hotspots of transcriptionfactor colocalization in the genome of Drosophila melanogaster[J]. Proc Natl Acad Sci USA,2006,103(32):12027-12032.
[26] Nègre N,Brown CD,Ma L,et al. A cis-regulatory map of theDrosophila genome[J]. Nature,2011,471(7339):527-531.
[27] Yan J,Enge M,Whitington T,et al. Transcription factor bindingin human cells occurs in dense clusters formed around cohesinanchor sites[J]. Cell,2013,154(4):801-813.