- Email: [email protected]
Genome architecture and expression
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Genome architecture and expression Editorial overview Frederick Alt and Genevieve Almouzni Current Opinion in Genetics & Development 2013, 23:79–80 For a complete overview see the Issue 0959-437X/$ – see front matter, Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.gde.2013.04.005
Frederick Alt Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA e-mail: [email protected] Frederick Alt is an Investigator of the Howard Hughes Medical Institute, the Charles A. Janeway Professor of Pediatrics and Professor of Genetics at Harvard Medical School and Director of the Program in Cellular and Molecular Medicine at Boston Children’s Hospital. He works on mechanisms of recombination, repair and genome stability in the context of immunology and cancer biology.
Genevieve Almouzni Department on Nuclear Dynamics, Institut Curie/Section de recherche, UMR218, 26, rue d’Ulm, 75231 Paris Cedex 05, France e-mail: [email protected] Genevieve Almouzni received her PhD from the Universite´ Pierre et Marie Curie, Paris, France, in 1988 and then pursued her training as a postdoctoral fellow in the laboratory of Alan Wolffe at the National Institutes of Health, Bethesda, USA. She is currently head of the department on nuclear dynamics at the Institut Curie in Paris, France. Her team has conducted research on chromatin dynamics, histone variants, histone chaperones and nuclear organization with a particular interest on heterochromatin and centromeres. Since 2009, she is Deputy Director in charge of advanced training for the Research Division at the Institut Curie.
www.sciencedirect.com
This volume focuses on the large-scale organization of the genome within the nucleus, and, particularly, on the relationship of this organization to chromosome function and genome stability during development. To address such questions, powerful new genome wide technologies recently have been developed and applied. Such technologies, including RNA-seq, ChIP-seq and 3C-based methods, in combination with advanced imaging studies and structural modeling, have offered new means to elucidate mechanisms by which chromatin components including RNA and protein factors control gene expression, replication, recombination, and the response to DNA damage. This work has provided new insights into ways in which nuclear compartmentalization, chromatin structure and three-dimensional genome organization contribute to regulating nuclear functions. An emerging focus of such studies is the elucidation of how such properties are propagated and maintained throughout cell division and in the face of DNA damage. These general questions have been addressed by many of the major experts in these fields as outlined below. The role of large-scale nuclear organization with respect to antigen receptor gene assembly from component gene segments illustrates how non-coding transcription of target DNA sequences provides a means to dictate the highly regulated assembly of different types of gene segments during the development of B and T lymphocytes. The review by Stubbington and Corcoran on ‘Non-coding transcription and largescale nuclear organisation of immunoglobulin recombination’ highlights the most recent discoveries on this topic. The geography of the genome in the nucleus becomes a parameter that has to be considered in the specific transcriptional programme associated with distinct cellular identities. Advances in this area are discussed by Hu¨bner et al. in the article on ‘Chromatin organization and transcriptional regulation’. The example of silent domains and their organization illustrates basic principles that can apply to budding yeast, nematodes and mammalian cells where the nuclear periphery represents a distinct compartment. This is discussed by Meister and Taddei in their article on ‘Building silent compartments at the nuclear periphery: a recurrent theme’. The theme of compartmentalization is further illustrated in the context of dynamic states during development to emphasize how it can actively participate in controlling developmental progression in the article by Lin and Murre on ‘Nuclear location and the control of developmental progression’. The model of X chromosome dosage in mammals offers a powerful system to analyze sexspecific regulation involving key features in chromatin organization during development as discussed by Schulz and Heard in the article on ‘Role and control of X chromosome dosage in mammalian development’. Finally, Guertin and Lis further address global aspects of transcriptional regulation in their article on ‘Mechanisms by which Current Opinion in Genetics & Development 2013, 23:79–80
80 Genome architecture and expression
transcription factors gain access to target sequence elements in chromatin’. Defining replication origins in order to reproduce the genomic information also exploits chromatin-based features. This is discussed by Me´chali et al. in the article on ‘Genetic and epigenetic determinants of DNA replication origins, position and activation’. Rearrangements at the heart of genome instability incorporate the importance of replication fork barriers as a driving force. Advances in model organisms such as yeast open up possibilities to link up these processes to chromatin dynamics. This is discussed by Lambert and Carr in the article on ‘Replication stress and genome rearrangements: lessons from yeast models’. How to propagate a particular chromatin state during replication has raised a number of issues and recent work highlights the complexity of players beyond histones. This is discussed by Whitehouse and Smith in the article on ‘Chromatin dynamics at the replication fork: there’s more to life than histones’. Following on the theme of genome stability, the definition of sites of recombination in meiosis has defined important role for chromatin-based mechanisms as presented by Borde and de Massy in the article on ‘Programmed induction of DNA double strand breaks during meiosis: Setting up communication between DNA and the chromosome structure’. The repair of DSBs and other types of DNA damage in eukaryotic cells occurs in the context of chromatin. In this context, recent advances continue to provide insights into the key roles that modifications of chromatin play in many aspects of DNA repair. Altmeyer and Lukas in the article on ‘To spread or not to spread — Chromatin modifications in response to DNA damage’ discuss new insights into feed-forward and feedback mechanisms by which
Current Opinion in Genetics & Development 2013, 23:79–80
mammalian cells regulate the extent of chromatin modifications after DNA damage and the role in repair pathway choice and fate of cells subsequent to genotoxic stress. Tsabar and Haber discuss chromatin remodeling in the context of checkpoint responses and DNA repair in Saccharomyces cerevisae in their article on ‘Chromatin modifications and chromatin remodeling during DNA repair in budding yeast’. Then, Seeber et al. go on in their article entitled ‘Nucleosome remodelers in double-strand break repair’ to discuss roles of remodelers and remodeling on DSB repair more broadly in Arabidopsis, yeast and mammalian cells, including discussing implications for the roles of such proteins in physical movement of chromatin subsequent to DNA damage in yeast. Several new technologies have helped to link 3D organization to function. A critical analysis of these approaches and the achievements obtained so far are presented in several pieces including ‘Chromatin organisation: form to function’ by de Graaf and van Steensel and the article on ‘Identical cells with different 3D genomes; cause and consequences?’ by Krijger and de Laat, as well as in the article on ‘Chromosomal domains: epigenetic contexts and functional implications of genomic compartmentalization’ by Tanay and Cavalli. To define chromosome topology, insulators, cohesion and condensin complexes have been leading the way. These advances have been discussed in the articles on ‘Condensin, cohesin and control of chromatin states’ by Aragon et al. and the article on the ‘The role of chromatin insulators in nuclear architecture and genome function’ by Van Bortle and Corces. Finally, the article on ‘Basic properties of epigenetic systems: lessons from the centromere’ by Go´mez-Rodrı´guez and Jansen describes how the centomere provides a paradigm to unravel basic principles in epigenetic inheritance.
www.sciencedirect.com
Genome architecture and expression Editorial overview Frederick Alt and Genevieve Almouzni Current Opinion in Genetics & Development 2013, 23:79–80 For a complete overview see the Issue 0959-437X/$ – see front matter, Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.gde.2013.04.005
Frederick Alt Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA e-mail: [email protected] Frederick Alt is an Investigator of the Howard Hughes Medical Institute, the Charles A. Janeway Professor of Pediatrics and Professor of Genetics at Harvard Medical School and Director of the Program in Cellular and Molecular Medicine at Boston Children’s Hospital. He works on mechanisms of recombination, repair and genome stability in the context of immunology and cancer biology.
Genevieve Almouzni Department on Nuclear Dynamics, Institut Curie/Section de recherche, UMR218, 26, rue d’Ulm, 75231 Paris Cedex 05, France e-mail: [email protected] Genevieve Almouzni received her PhD from the Universite´ Pierre et Marie Curie, Paris, France, in 1988 and then pursued her training as a postdoctoral fellow in the laboratory of Alan Wolffe at the National Institutes of Health, Bethesda, USA. She is currently head of the department on nuclear dynamics at the Institut Curie in Paris, France. Her team has conducted research on chromatin dynamics, histone variants, histone chaperones and nuclear organization with a particular interest on heterochromatin and centromeres. Since 2009, she is Deputy Director in charge of advanced training for the Research Division at the Institut Curie.
www.sciencedirect.com
This volume focuses on the large-scale organization of the genome within the nucleus, and, particularly, on the relationship of this organization to chromosome function and genome stability during development. To address such questions, powerful new genome wide technologies recently have been developed and applied. Such technologies, including RNA-seq, ChIP-seq and 3C-based methods, in combination with advanced imaging studies and structural modeling, have offered new means to elucidate mechanisms by which chromatin components including RNA and protein factors control gene expression, replication, recombination, and the response to DNA damage. This work has provided new insights into ways in which nuclear compartmentalization, chromatin structure and three-dimensional genome organization contribute to regulating nuclear functions. An emerging focus of such studies is the elucidation of how such properties are propagated and maintained throughout cell division and in the face of DNA damage. These general questions have been addressed by many of the major experts in these fields as outlined below. The role of large-scale nuclear organization with respect to antigen receptor gene assembly from component gene segments illustrates how non-coding transcription of target DNA sequences provides a means to dictate the highly regulated assembly of different types of gene segments during the development of B and T lymphocytes. The review by Stubbington and Corcoran on ‘Non-coding transcription and largescale nuclear organisation of immunoglobulin recombination’ highlights the most recent discoveries on this topic. The geography of the genome in the nucleus becomes a parameter that has to be considered in the specific transcriptional programme associated with distinct cellular identities. Advances in this area are discussed by Hu¨bner et al. in the article on ‘Chromatin organization and transcriptional regulation’. The example of silent domains and their organization illustrates basic principles that can apply to budding yeast, nematodes and mammalian cells where the nuclear periphery represents a distinct compartment. This is discussed by Meister and Taddei in their article on ‘Building silent compartments at the nuclear periphery: a recurrent theme’. The theme of compartmentalization is further illustrated in the context of dynamic states during development to emphasize how it can actively participate in controlling developmental progression in the article by Lin and Murre on ‘Nuclear location and the control of developmental progression’. The model of X chromosome dosage in mammals offers a powerful system to analyze sexspecific regulation involving key features in chromatin organization during development as discussed by Schulz and Heard in the article on ‘Role and control of X chromosome dosage in mammalian development’. Finally, Guertin and Lis further address global aspects of transcriptional regulation in their article on ‘Mechanisms by which Current Opinion in Genetics & Development 2013, 23:79–80
80 Genome architecture and expression
transcription factors gain access to target sequence elements in chromatin’. Defining replication origins in order to reproduce the genomic information also exploits chromatin-based features. This is discussed by Me´chali et al. in the article on ‘Genetic and epigenetic determinants of DNA replication origins, position and activation’. Rearrangements at the heart of genome instability incorporate the importance of replication fork barriers as a driving force. Advances in model organisms such as yeast open up possibilities to link up these processes to chromatin dynamics. This is discussed by Lambert and Carr in the article on ‘Replication stress and genome rearrangements: lessons from yeast models’. How to propagate a particular chromatin state during replication has raised a number of issues and recent work highlights the complexity of players beyond histones. This is discussed by Whitehouse and Smith in the article on ‘Chromatin dynamics at the replication fork: there’s more to life than histones’. Following on the theme of genome stability, the definition of sites of recombination in meiosis has defined important role for chromatin-based mechanisms as presented by Borde and de Massy in the article on ‘Programmed induction of DNA double strand breaks during meiosis: Setting up communication between DNA and the chromosome structure’. The repair of DSBs and other types of DNA damage in eukaryotic cells occurs in the context of chromatin. In this context, recent advances continue to provide insights into the key roles that modifications of chromatin play in many aspects of DNA repair. Altmeyer and Lukas in the article on ‘To spread or not to spread — Chromatin modifications in response to DNA damage’ discuss new insights into feed-forward and feedback mechanisms by which
Current Opinion in Genetics & Development 2013, 23:79–80
mammalian cells regulate the extent of chromatin modifications after DNA damage and the role in repair pathway choice and fate of cells subsequent to genotoxic stress. Tsabar and Haber discuss chromatin remodeling in the context of checkpoint responses and DNA repair in Saccharomyces cerevisae in their article on ‘Chromatin modifications and chromatin remodeling during DNA repair in budding yeast’. Then, Seeber et al. go on in their article entitled ‘Nucleosome remodelers in double-strand break repair’ to discuss roles of remodelers and remodeling on DSB repair more broadly in Arabidopsis, yeast and mammalian cells, including discussing implications for the roles of such proteins in physical movement of chromatin subsequent to DNA damage in yeast. Several new technologies have helped to link 3D organization to function. A critical analysis of these approaches and the achievements obtained so far are presented in several pieces including ‘Chromatin organisation: form to function’ by de Graaf and van Steensel and the article on ‘Identical cells with different 3D genomes; cause and consequences?’ by Krijger and de Laat, as well as in the article on ‘Chromosomal domains: epigenetic contexts and functional implications of genomic compartmentalization’ by Tanay and Cavalli. To define chromosome topology, insulators, cohesion and condensin complexes have been leading the way. These advances have been discussed in the articles on ‘Condensin, cohesin and control of chromatin states’ by Aragon et al. and the article on the ‘The role of chromatin insulators in nuclear architecture and genome function’ by Van Bortle and Corces. Finally, the article on ‘Basic properties of epigenetic systems: lessons from the centromere’ by Go´mez-Rodrı´guez and Jansen describes how the centomere provides a paradigm to unravel basic principles in epigenetic inheritance.
www.sciencedirect.com