The regulatory landscape of Drosophila imaginal disc regeneration

[eng] One of the most important questions in regenerative biology is how and when genes change expression to trigger regeneration programs. Resetting of gene expression patterns during injury responses is shaped by the coordinated action of genomic regions that integrate the activity of multiple sequence-specific DNA binding proteins. Using genome-wide approaches to interrogate chromatin function we identify the regulatory elements governing tissue recovery in Drosophila imaginal discs, which show a high regenerative capacity after genetically induced cell death. Our findings indicate a global co-regulation of gene expression as well as the existence of a regeneration program driven by different types of regulatory elements. Novel enhancers acting exclusively in the damaged tissue cooperate with enhancers co-opted from other tissues and developmental stages, and with endogenous enhancers that show increased activity after injury. These enhancers host binding sites for regulatory proteins, including a core set of conserved transcription factors that regulate regeneration across metazoans.[cat] Una de les preguntes més freqüents en el camp de la biologia regenerativa és com i quan els gens poden canviar els seus patrons d’expressió per accionar els programes gènics requerits a la regeneració. Durant la resposta al dany, els patrons d’expressió dels gens son re-iniciats, en part, gràcies a la funció coordinada de regions genòmiques reguladores. Aquestes, integren l’activitat de diferents proteïnes d’unió a seqüències específiques de l’ADN. Mitjançant l'ús de tècniques d’anàlisi massiva hem interrogat la funció de la cromatina i hem identificat les regions reguladores encarregades de dur a terme la regeneració dels discos imaginals de Drosophila. Aquests són estructures primordials que presenten una elevada capacitat regenerativa rere la inducció de mort cel·lular per ablació genètica. Els nostres resultats indiquen que durant la regeneració hi ha co-regulació de l’expressió gènica i que els programes regeneratius són orquestrats per diferents classes de regions reguladores. Els novel enhancers actuen exclusivament durant la regeneració i cooperen amb enhancers reclutats d’altres teixits o estadis del desenvolupament, així com amb enhancers endògens que presenten una elevada accessibilitat en resposta al dany. Els tres tipus d’elements reguladors presenten seqüències específiques per proteïnes d’unió l’ADN, incloent un set de factors de transcripció que no només es troba conservat però també requerit a la regeneració a través dels metazoas

Chromatin dynamics in regeneration epithelia: lessons from Drosophila imaginal discs

During the process of regeneration, a switch in the transcription program occurs in cells that contribute to the reconstruction of the missing tissue. Early signals released upon damage are integrated into the chromatin of responding cells to change its activity and function. Changes in chromatin dynamics result in transcriptional reprogramming, this is the coordinated regulation of expression of a specific subset of genes required for the regeneration process. Here we summarize changes in gene expression and chromatin dynamics that occurs during the process of regeneration of Drosophila imaginal discs

Damage- responsive elements in Drosophila regeneration

One of the most important questions in regenerative biology is to unveil how and when genes change expression and trigger regeneration programs. The resetting of gene expression patterns during response to injury is governed by coordinated actions of genomic regions that control the activity of multiple sequence-specific DNA binding proteins. Using genome-wide approaches to interrogate chromatin function, we here identify the elements that regulate tissue recovery in Drosophila imaginal discs, which show a high regenerative capacity after genetically induced cell death. Our findings indicate there is global coregulation of gene expression as well as a regeneration program driven by different types of regulatory elements. Novel enhancers acting exclusively within damaged tissue cooperate with enhancers co-opted from other tissues and other developmental stages, as well as with endogenous enhancers that show increased activity after injury. Together, these enhancers host binding sites for regulatory proteins that include a core set of conserved transcription factors that control regeneration across metazoans

Damage-responsive elements in Drosophila regeneration

One of the most important questions in regenerative biology is to unveil how and when genes change expression and trigger regeneration programs. The resetting of gene expression patterns during response to injury is governed by coordinated actions of genomic regions that control the activity of multiple sequence-specific DNA binding proteins. Using genome-wide approaches to interrogate chromatin function, we here identify the elements that regulate tissue recovery in Drosophila imaginal discs, which show a high regenerative capacity after genetically induced cell death. Our findings indicate there is global coregulation of gene expression as well as a regeneration program driven by different types of regulatory elements. Novel enhancers acting exclusively within damaged tissue cooperate with enhancers co-opted from other tissues and other developmental stages, as well as with endogenous enhancers that show increased activity after injury. Together, these enhancers host binding sites for regulatory proteins that include a core set of conserved transcription factors that control regeneration across metazoans.This project was funded by the following grants: PCIN-2013-048 from the Spanish Ministerio de Economía y Competitividad and the Institució Catalana de Recerca i Estudis Avançats (via an ICREA Academia award) to M.C.; BFU2012-36888 and BFU2015-67623-P from the Spanish Ministerio de Economía y Competitividad to F.S. and M.C.; the European Research Council/European Community's Seventh Framework Programme grant 294653 RNA-MAPS, the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, the Spanish Ministry of Economy and Competitiveness (MEC) “Centro de Excelencia Severo Ochoa,” and the CERCA Programme / Generalitat de Catalunya to R.G

Damage-responsive elements in Drosophila regeneration

One of the most important questions in regenerative biology is to unveil how and when genes change expression and trigger regeneration programs. The resetting of gene expression patterns during response to injury is governed by coordinated actions of genomic regions that control the activity of multiple sequence-specific DNA binding proteins. Using genome-wide approaches to interrogate chromatin function, we here identify the elements that regulate tissue recovery in Drosophila imaginal discs, which show a high regenerative capacity after genetically induced cell death. Our findings indicate there is global coregulation of gene expression as well as a regeneration program driven by different types of regulatory elements. Novel enhancers acting exclusively within damaged tissue cooperate with enhancers co-opted from other tissues and other developmental stages, as well as with endogenous enhancers that show increased activity after injury. Together, these enhancers host binding sites for regulatory proteins that include a core set of conserved transcription factors that control regeneration across metazoans.This project was funded by the following grants: PCIN-2013-048 from the Spanish Ministerio de Economía y Competitividad and the Institució Catalana de Recerca i Estudis Avançats (via an ICREA Academia award) to M.C.; BFU2012-36888 and BFU2015-67623-P from the Spanish Ministerio de Economía y Competitividad to F.S. and M.C.; the European Research Council/European Community's Seventh Framework Programme grant 294653 RNA-MAPS, the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, the Spanish Ministry of Economy and Competitiveness (MEC) “Centro de Excelencia Severo Ochoa,” and the CERCA Programme / Generalitat de Catalunya to R.G

The DUNE Far Detector Vertical Drift Technology, Technical Design Report

International audienceDUNE is an international experiment dedicated to addressing some of the questions at the forefront of particle physics and astrophysics, including the mystifying preponderance of matter over antimatter in the early universe. The dual-site experiment will employ an intense neutrino beam focused on a near and a far detector as it aims to determine the neutrino mass hierarchy and to make high-precision measurements of the PMNS matrix parameters, including the CP-violating phase. It will also stand ready to observe supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector implements liquid argon time-projection chamber (LArTPC) technology, and combines the many tens-of-kiloton fiducial mass necessary for rare event searches with the sub-centimeter spatial resolution required to image those events with high precision. The addition of a photon detection system enhances physics capabilities for all DUNE physics drivers and opens prospects for further physics explorations. Given its size, the far detector will be implemented as a set of modules, with LArTPC designs that differ from one another as newer technologies arise. In the vertical drift LArTPC design, a horizontal cathode bisects the detector, creating two stacked drift volumes in which ionization charges drift towards anodes at either the top or bottom. The anodes are composed of perforated PCB layers with conductive strips, enabling reconstruction in 3D. Light-trap-style photon detection modules are placed both on the cryostat's side walls and on the central cathode where they are optically powered. This Technical Design Report describes in detail the technical implementations of each subsystem of this LArTPC that, together with the other far detector modules and the near detector, will enable DUNE to achieve its physics goals

The DUNE Far Detector Vertical Drift Technology, Technical Design Report

International audienceDUNE is an international experiment dedicated to addressing some of the questions at the forefront of particle physics and astrophysics, including the mystifying preponderance of matter over antimatter in the early universe. The dual-site experiment will employ an intense neutrino beam focused on a near and a far detector as it aims to determine the neutrino mass hierarchy and to make high-precision measurements of the PMNS matrix parameters, including the CP-violating phase. It will also stand ready to observe supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector implements liquid argon time-projection chamber (LArTPC) technology, and combines the many tens-of-kiloton fiducial mass necessary for rare event searches with the sub-centimeter spatial resolution required to image those events with high precision. The addition of a photon detection system enhances physics capabilities for all DUNE physics drivers and opens prospects for further physics explorations. Given its size, the far detector will be implemented as a set of modules, with LArTPC designs that differ from one another as newer technologies arise. In the vertical drift LArTPC design, a horizontal cathode bisects the detector, creating two stacked drift volumes in which ionization charges drift towards anodes at either the top or bottom. The anodes are composed of perforated PCB layers with conductive strips, enabling reconstruction in 3D. Light-trap-style photon detection modules are placed both on the cryostat's side walls and on the central cathode where they are optically powered. This Technical Design Report describes in detail the technical implementations of each subsystem of this LArTPC that, together with the other far detector modules and the near detector, will enable DUNE to achieve its physics goals

The DUNE Far Detector Vertical Drift Technology, Technical Design Report

International audienceDUNE is an international experiment dedicated to addressing some of the questions at the forefront of particle physics and astrophysics, including the mystifying preponderance of matter over antimatter in the early universe. The dual-site experiment will employ an intense neutrino beam focused on a near and a far detector as it aims to determine the neutrino mass hierarchy and to make high-precision measurements of the PMNS matrix parameters, including the CP-violating phase. It will also stand ready to observe supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector implements liquid argon time-projection chamber (LArTPC) technology, and combines the many tens-of-kiloton fiducial mass necessary for rare event searches with the sub-centimeter spatial resolution required to image those events with high precision. The addition of a photon detection system enhances physics capabilities for all DUNE physics drivers and opens prospects for further physics explorations. Given its size, the far detector will be implemented as a set of modules, with LArTPC designs that differ from one another as newer technologies arise. In the vertical drift LArTPC design, a horizontal cathode bisects the detector, creating two stacked drift volumes in which ionization charges drift towards anodes at either the top or bottom. The anodes are composed of perforated PCB layers with conductive strips, enabling reconstruction in 3D. Light-trap-style photon detection modules are placed both on the cryostat's side walls and on the central cathode where they are optically powered. This Technical Design Report describes in detail the technical implementations of each subsystem of this LArTPC that, together with the other far detector modules and the near detector, will enable DUNE to achieve its physics goals

The DUNE Far Detector Vertical Drift Technology, Technical Design Report

DUNE is an international experiment dedicated to addressing some of the questions at the forefront of particle physics and astrophysics, including the mystifying preponderance of matter over antimatter in the early universe. The dual-site experiment will employ an intense neutrino beam focused on a near and a far detector as it aims to determine the neutrino mass hierarchy and to make high-precision measurements of the PMNS matrix parameters, including the CP-violating phase. It will also stand ready to observe supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector implements liquid argon time-projection chamber (LArTPC) technology, and combines the many tens-of-kiloton fiducial mass necessary for rare event searches with the sub-centimeter spatial resolution required to image those events with high precision. The addition of a photon detection system enhances physics capabilities for all DUNE physics drivers and opens prospects for further physics explorations. Given its size, the far detector will be implemented as a set of modules, with LArTPC designs that differ from one another as newer technologies arise. In the vertical drift LArTPC design, a horizontal cathode bisects the detector, creating two stacked drift volumes in which ionization charges drift towards anodes at either the top or bottom. The anodes are composed of perforated PCB layers with conductive strips, enabling reconstruction in 3D. Light-trap-style photon detection modules are placed both on the cryostat's side walls and on the central cathode where they are optically powered. This Technical Design Report describes in detail the technical implementations of each subsystem of this LArTPC that, together with the other far detector modules and the near detector, will enable DUNE to achieve its physics goals