Cooperativity, Specificity, and Evolutionary Stability of Polycomb Targeting in Drosophila
Summary: Metazoan genomes are partitioned into modular chromosomal domains containing active or repressive chromatin. In flies, Polycomb group (PcG) response elements (PREs) recruit PHO and other DNA-binding factors and act as nucleation sites for the formation of Polycomb repressive domains. The se...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714007645 |
| _version_ | 1828393248733790208 |
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| author | Bernd Schuettengruber Noa Oded Elkayam Tom Sexton Marianne Entrevan Shani Stern Aubin Thomas Eitan Yaffe Hugues Parrinello Amos Tanay Giacomo Cavalli |
| author_facet | Bernd Schuettengruber Noa Oded Elkayam Tom Sexton Marianne Entrevan Shani Stern Aubin Thomas Eitan Yaffe Hugues Parrinello Amos Tanay Giacomo Cavalli |
| author_sort | Bernd Schuettengruber |
| collection | DOAJ |
| description | Summary: Metazoan genomes are partitioned into modular chromosomal domains containing active or repressive chromatin. In flies, Polycomb group (PcG) response elements (PREs) recruit PHO and other DNA-binding factors and act as nucleation sites for the formation of Polycomb repressive domains. The sequence specificity of PREs is not well understood. Here, we use comparative epigenomics and transgenic assays to show that Drosophila domain organization and PRE specification are evolutionarily conserved despite significant cis-element divergence within Polycomb domains, whereas cis-element evolution is strongly correlated with transcription factor binding divergence outside of Polycomb domains. Cooperative interactions of PcG complexes and their recruiting factor PHO stabilize PHO recruitment to low-specificity sequences. Consistently, PHO recruitment to sites within Polycomb domains is stabilized by PRC1. These data suggest that cooperative rather than hierarchical interactions among low-affinity sequences, DNA-binding factors, and the Polycomb machinery are giving rise to specific and strongly conserved 3D structures in Drosophila. : Schuettengruber et al. present an extensive comparative epigenomics data set, providing new insights into cis-driven versus buffered evolution of Polycomb recruitment and Polycomb domain specificity. Using chromatin immunoprecipitation sequencing and transgenic assays, they demonstrate an extremely high conservation of Polycomb repressive domains in five Drosophila species. Using Hi-C and knockout experiments, they challenge the standard hierarchical Polycomb recruitment model and demonstrate that cooperative rather than hierarchical interactions among DNA motifs, transcription factors, and Polycomb group complexes define Polycomb domains. |
| first_indexed | 2024-12-10T07:34:38Z |
| format | Article |
| id | doaj.art-f8b47411ec334a6897994fd26f0065e2 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T07:34:38Z |
| publishDate | 2014-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-f8b47411ec334a6897994fd26f0065e22022-12-22T01:57:27ZengElsevierCell Reports2211-12472014-10-0191219233Cooperativity, Specificity, and Evolutionary Stability of Polycomb Targeting in DrosophilaBernd Schuettengruber0Noa Oded Elkayam1Tom Sexton2Marianne Entrevan3Shani Stern4Aubin Thomas5Eitan Yaffe6Hugues Parrinello7Amos Tanay8Giacomo Cavalli9Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, FranceDepartment of Computer Science and Applied Mathematics and Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 7610001, IsraelInstitute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, FranceInstitute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, FranceDepartment of Computer Science and Applied Mathematics and Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 7610001, IsraelInstitute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, FranceDepartment of Computer Science and Applied Mathematics and Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 7610001, IsraelMontpellier GenomiX IBiSA, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, FranceDepartment of Computer Science and Applied Mathematics and Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 7610001, Israel; Corresponding authorInstitute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France; Corresponding authorSummary: Metazoan genomes are partitioned into modular chromosomal domains containing active or repressive chromatin. In flies, Polycomb group (PcG) response elements (PREs) recruit PHO and other DNA-binding factors and act as nucleation sites for the formation of Polycomb repressive domains. The sequence specificity of PREs is not well understood. Here, we use comparative epigenomics and transgenic assays to show that Drosophila domain organization and PRE specification are evolutionarily conserved despite significant cis-element divergence within Polycomb domains, whereas cis-element evolution is strongly correlated with transcription factor binding divergence outside of Polycomb domains. Cooperative interactions of PcG complexes and their recruiting factor PHO stabilize PHO recruitment to low-specificity sequences. Consistently, PHO recruitment to sites within Polycomb domains is stabilized by PRC1. These data suggest that cooperative rather than hierarchical interactions among low-affinity sequences, DNA-binding factors, and the Polycomb machinery are giving rise to specific and strongly conserved 3D structures in Drosophila. : Schuettengruber et al. present an extensive comparative epigenomics data set, providing new insights into cis-driven versus buffered evolution of Polycomb recruitment and Polycomb domain specificity. Using chromatin immunoprecipitation sequencing and transgenic assays, they demonstrate an extremely high conservation of Polycomb repressive domains in five Drosophila species. Using Hi-C and knockout experiments, they challenge the standard hierarchical Polycomb recruitment model and demonstrate that cooperative rather than hierarchical interactions among DNA motifs, transcription factors, and Polycomb group complexes define Polycomb domains.http://www.sciencedirect.com/science/article/pii/S2211124714007645 |
| spellingShingle | Bernd Schuettengruber Noa Oded Elkayam Tom Sexton Marianne Entrevan Shani Stern Aubin Thomas Eitan Yaffe Hugues Parrinello Amos Tanay Giacomo Cavalli Cooperativity, Specificity, and Evolutionary Stability of Polycomb Targeting in Drosophila Cell Reports |
| title | Cooperativity, Specificity, and Evolutionary Stability of Polycomb Targeting in Drosophila |
| title_full | Cooperativity, Specificity, and Evolutionary Stability of Polycomb Targeting in Drosophila |
| title_fullStr | Cooperativity, Specificity, and Evolutionary Stability of Polycomb Targeting in Drosophila |
| title_full_unstemmed | Cooperativity, Specificity, and Evolutionary Stability of Polycomb Targeting in Drosophila |
| title_short | Cooperativity, Specificity, and Evolutionary Stability of Polycomb Targeting in Drosophila |
| title_sort | cooperativity specificity and evolutionary stability of polycomb targeting in drosophila |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714007645 |
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