Borders of Cis-Regulatory DNA Sequences Preferentially Harbor the Divergent Transcription Factor Binding Motifs in the Human Genome
Changes in cis-regulatory DNA sequences and transcription factor (TF) repertoires provide major sources of phenotypic diversity that shape the evolution of gene regulation in eukaryotes. The DNA-binding specificities of TFs may be diversified or produce new variants in different eukaryotic species....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2018.00571/full |
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| author | Jia-Hsin Huang Ryan Shun-Yuen Kwan Zing Tsung-Yeh Tsai Tzu-Chieh Lin Huai-Kuang Tsai |
| author_facet | Jia-Hsin Huang Ryan Shun-Yuen Kwan Zing Tsung-Yeh Tsai Tzu-Chieh Lin Huai-Kuang Tsai |
| author_sort | Jia-Hsin Huang |
| collection | DOAJ |
| description | Changes in cis-regulatory DNA sequences and transcription factor (TF) repertoires provide major sources of phenotypic diversity that shape the evolution of gene regulation in eukaryotes. The DNA-binding specificities of TFs may be diversified or produce new variants in different eukaryotic species. However, it is currently unclear how various levels of divergence in TF DNA-binding specificities or motifs became introduced into the cis-regulatory DNA regions of the genome over evolutionary time. Here, we first estimated the evolutionary divergence levels of TF binding motifs and quantified their occurrence at DNase I-hypersensitive sites. Results from our in silico motif scan and experimentally derived chromatin immunoprecipitation (TF-ChIP) show that the divergent motifs tend to be introduced in the edges of cis-regulatory regions, which is probably accompanied by the expansion of the accessible core of promoter-associated regulatory elements during evolution. We also find that the genes neighboring the expanded cis-regulatory regions with the most divergent motifs are associated with functions like development and morphogenesis. Accordingly, we propose that the accumulation of divergent motifs in the edges of cis-regulatory regions provides a functional mechanism for the evolution of divergent regulatory circuits. |
| first_indexed | 2024-12-10T12:33:16Z |
| format | Article |
| id | doaj.art-5602c23704c84bdf9b545bbbdcf1de31 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-10T12:33:16Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-5602c23704c84bdf9b545bbbdcf1de312022-12-22T01:48:45ZengFrontiers Media S.A.Frontiers in Genetics1664-80212018-11-01910.3389/fgene.2018.00571423489Borders of Cis-Regulatory DNA Sequences Preferentially Harbor the Divergent Transcription Factor Binding Motifs in the Human GenomeJia-Hsin Huang0Ryan Shun-Yuen Kwan1Zing Tsung-Yeh Tsai2Tzu-Chieh Lin3Huai-Kuang Tsai4Institute of Information Science, Academia Sinica, Nankang, Taipei, TaiwanInstitute of Information Science, Academia Sinica, Nankang, Taipei, TaiwanDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United StatesInstitute of Information Science, Academia Sinica, Nankang, Taipei, TaiwanInstitute of Information Science, Academia Sinica, Nankang, Taipei, TaiwanChanges in cis-regulatory DNA sequences and transcription factor (TF) repertoires provide major sources of phenotypic diversity that shape the evolution of gene regulation in eukaryotes. The DNA-binding specificities of TFs may be diversified or produce new variants in different eukaryotic species. However, it is currently unclear how various levels of divergence in TF DNA-binding specificities or motifs became introduced into the cis-regulatory DNA regions of the genome over evolutionary time. Here, we first estimated the evolutionary divergence levels of TF binding motifs and quantified their occurrence at DNase I-hypersensitive sites. Results from our in silico motif scan and experimentally derived chromatin immunoprecipitation (TF-ChIP) show that the divergent motifs tend to be introduced in the edges of cis-regulatory regions, which is probably accompanied by the expansion of the accessible core of promoter-associated regulatory elements during evolution. We also find that the genes neighboring the expanded cis-regulatory regions with the most divergent motifs are associated with functions like development and morphogenesis. Accordingly, we propose that the accumulation of divergent motifs in the edges of cis-regulatory regions provides a functional mechanism for the evolution of divergent regulatory circuits.https://www.frontiersin.org/article/10.3389/fgene.2018.00571/fulltranscription factor binding sitesmotifscis-regulatory elementsTF binding specificitiesopen chromatins |
| spellingShingle | Jia-Hsin Huang Ryan Shun-Yuen Kwan Zing Tsung-Yeh Tsai Tzu-Chieh Lin Huai-Kuang Tsai Borders of Cis-Regulatory DNA Sequences Preferentially Harbor the Divergent Transcription Factor Binding Motifs in the Human Genome Frontiers in Genetics transcription factor binding sites motifs cis-regulatory elements TF binding specificities open chromatins |
| title | Borders of Cis-Regulatory DNA Sequences Preferentially Harbor the Divergent Transcription Factor Binding Motifs in the Human Genome |
| title_full | Borders of Cis-Regulatory DNA Sequences Preferentially Harbor the Divergent Transcription Factor Binding Motifs in the Human Genome |
| title_fullStr | Borders of Cis-Regulatory DNA Sequences Preferentially Harbor the Divergent Transcription Factor Binding Motifs in the Human Genome |
| title_full_unstemmed | Borders of Cis-Regulatory DNA Sequences Preferentially Harbor the Divergent Transcription Factor Binding Motifs in the Human Genome |
| title_short | Borders of Cis-Regulatory DNA Sequences Preferentially Harbor the Divergent Transcription Factor Binding Motifs in the Human Genome |
| title_sort | borders of cis regulatory dna sequences preferentially harbor the divergent transcription factor binding motifs in the human genome |
| topic | transcription factor binding sites motifs cis-regulatory elements TF binding specificities open chromatins |
| url | https://www.frontiersin.org/article/10.3389/fgene.2018.00571/full |
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