Suchergebnisse

The unicellular ancestor of animals had a complex repertoire of genes linked to multicellular processes. This suggests that changes in the regulatory genome, rather than in gene innovation, were key to the origin of animals. Here, we carry out multiple functional genomic assays in Capsaspora owczarzaki, the unicellular relative of animals with the largest known gene repertoire for transcriptional regulation. We show that changing chromatin states, differential lincRNA expression, and dynamic cis-regulatory sites are associated with life cycle transitions in Capsaspora. Moreover, we demonstrate conservation of animal developmental transcription-factor networks and extensive network interconnection in this premetazoan organism. In contrast, however, Capsaspora lacks animal promoter types, and its regulatory sites are small, proximal, and lack signatures of animal enhancers. Overall, our results indicate that the emergence of animal multicellularity was linked to a major shift in genome cis-regulatory complexity, most notably the appearance of distal enhancer regulation. ; This work was supported by an Institució Catalana de Recerca i Estudis Avançats contract, a European Research Council Consolidator Grant (ERC-2012-Co-616960), and a grant from Ministerio de Economía y Competitividad (MINECO) (BFU-2011-23434) (to I.R.-T.). We also acknowledge financial support from Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement de la Generalitat de Catalunya (project 2014 SGR 619). The work in L.D.'s laboratory was supported by grants from the Spanish "Ministerio de Educación y Ciencia" (SAF2013-48926-P), AGAUR, and the European Commission's 7th Framework Program 4DCellFate (277899). A.S.-P. is supported by an EMBO Long-Term Fellowship (ALTF 841-2014). J.L.G.-S. was funded by grants from Ministerio de Economía y Competitividad (BFU2013-41322-P) and the Andalusian Government (BIO-396). J.J.T. has a postdoctoral grant from the University Pablo de Olavide. The CRG/UPF Proteomics Unit is part of the "Plataforma de Recursos Biomoleculares y Bioinformáticos (ProteoRed)" supported by a grant from Instituto de Salud Carlos III (ISCIII) (PT13/0001). ; Peer reviewed

Cell-specific regulation of protein levels and activity is essential for the distribution of functions among multiple cell types in animals. The finding that many genes involved in these regulatory processes have a premetazoan origin raises the intriguing possibility that the mechanisms required for spatially regulated cell differentiation evolved prior to the appearance of animals. Here, we use high-throughput proteomics in Capsaspora owczarzaki, a close unicellular relative of animals, to characterize the dynamic proteome and phosphoproteome profiles of three temporally distinct cell types in this premetazoan species. We show that life-cycle transitions are linked to extensive proteome and phosphoproteome remodeling and that they affect key genes involved in animal multicellularity, such as transcription factors and tyrosine kinases. The observation of shared features between Capsaspora and metazoans indicates that elaborate and conserved phosphosignaling and proteome regulation supported temporal cell-type differentiation in the unicellular ancestor of animals. ; The CRG/UPF Proteomics Unit is part of the "Plataforma de Recursos Biomoleculares y Bioinformáticos (ProteoRed)" supported by grant PT13/0001 of Instituto de Salud Carlos III (ISCIII). A.S.-P. is supported by an EMBO Long-Term Fellowship (ALTF 841-2014). T.G. group research is funded in part by a grant from the Spanish Ministry of Economy and Competitiveness (BIO2012-37161), a grant from the Qatar National Research Fund (NPRP 5-298-3-086), a grant from the European Union FP7 FP7-PEOPLE-2013-ITN-606786, and a grant from the European Research Council under the European Union's Seventh Framework Program (FP/2007-2013)/ERC (grant agreement no. ERC-2012-StG-310325). I.R.-T. group research is supported by an Institució Catalana de Recerca i Estudis Avançats contract, a European Research Council Consolidator Grant (ERC-2012-Co-616960), and a grant (BFU-2011-23434) from Ministerio de Economía y Competitividad (MINECO). I.R.-T. also acknowledges financial support from Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement de la Generalitat de Catalunya (Project 2014 SGR 619 and Project 2014 SGR 678)

The unicellular ancestor of animals had a complex repertoire of genes linked to multicellular processes. This suggests that changes in the regulatory genome, rather than in gene innovation, were key to the origin of animals. Here, we carry out multiple functional genomic assays in Capsaspora owczarzaki, the unicellular relative of animals with the largest known gene repertoire for transcriptional regulation. We show that changing chromatin states, differential lincRNA expression, and dynamic cis-regulatory sites are associated with life cycle transitions in Capsaspora. Moreover, we demonstrate conservation of animal developmental transcription-factor networks and extensive network interconnection in this premetazoan organism. In contrast, however, Capsaspora lacks animal promoter types, and its regulatory sites are small, proximal, and lack signatures of animal enhancers. Overall, our results indicate that the emergence of animal multicellularity was linked to a major shift in genome cis-regulatory complexity, most notably the appearance of distal enhancer regulation. ; This work was supported by an Institució Catalana de Recerca i Estudis Avançats contract, a European Research Council Consolidator Grant (ERC-2012-Co-616960), and a grant from Ministerio de Economía y Competitividad (MINECO) (BFU-2011-23434) (to I.R.-T.). We also acknowledge financial support from Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement de la Generalitat de Catalunya (project 2014 SGR 619). The work in L.D.'s laboratory was supported by grants from the Spanish "Ministerio de Educación y Ciencia" (SAF2013-48926-P), AGAUR, and the European Commission's 7th Framework Program 4DCellFate (277899). A.S.-P. is supported by an EMBO Long-Term Fellowship (ALTF 841-2014). J.L.G.-S. was funded by grants from Ministerio de Economía y Competitividad (BFU2013-41322-P) and the Andalusian Government (BIO-396). J.J.T. has a postdoctoral grant from the University Pablo de Olavide. The CRG/UPF Proteomics Unit is part of the "Plataforma de Recursos Biomoleculares y Bioinformáticos (ProteoRed)" supported by a grant from Instituto de Salud Carlos III (ISCIII) (PT13/0001). We thank Guadalupe Espadas for her support with the histone derivatization protocol and Núria Ros and Meritxell Antó for technical support. Finally, we thank the CRG Genomics Unit for helping with ChIP-seq and RNA-seq sequencing.