Histone hyperacetylation disrupts core gene regulatory architecture in rhabdomyosarcoma

Core regulatory transcription factors (CR TFs) orchestrate the placement of super-enhancers (SEs) to activate transcription of cell-identity specifying gene networks, and are critical in promoting cancer. Here, we define the core regulatory circuitry of rhabdomyosarcoma and identify critical CR TF dependencies. These CR TFs build SEs that have the highest levels of histone acetylation, yet paradoxically the same SEs also harbor the greatest amounts of histone deacetylases. We find that hyperacetylation selectively halts CR TF transcription. To investigate the architectural determinants of this phenotype, we used absolute quantification of architecture (AQuA) HiChIP, which revealed erosion of native SE contacts, and aberrant spreading of contacts that involved histone acetylation. Hyperacetylation removes RNA polymerase II (RNA Pol II) from core regulatory genetic elements, and eliminates RNA Pol II but not BRD4 phase condensates. This study identifies an SE-specific requirement for balancing histone modification states to maintain SE architecture and CR TF transcription

High Energy Physics Opportunities Using Reactor Antineutrinos

Nuclear reactors are uniquely powerful, abundant, and flavor-pure sources of antineutrinos that continue to play a vital role in the US neutrino physics program. The US reactor antineutrino physics community is a diverse interest group encompassing many detection technologies and many particle physics topics, including Standard Model and short-baseline oscillations, BSM physics searches, and reactor flux and spectrum modeling. The community's aims offer strong complimentary with numerous aspects of the wider US neutrino program and have direct relevance to most of the topical sub-groups composing the Snowmass 2021 Neutrino Frontier. Reactor neutrino experiments also have a direct societal impact and have become a strong workforce and technology development pipeline for DOE National Laboratories and universities. This white paper, prepared as a submission to the Snowmass 2021 community organizing exercise, will survey the state of the reactor antineutrino physics field and summarize the ways in which current and future reactor antineutrino experiments can play a critical role in advancing the field of particle physics in the next decade

High Energy Physics Opportunities Using Reactor Antineutrinos

Nuclear reactors are uniquely powerful, abundant, and flavor-pure sources of antineutrinos that continue to play a vital role in the US neutrino physics program. The US reactor antineutrino physics community is a diverse interest group encompassing many detection technologies and many particle physics topics, including Standard Model and short-baseline oscillations, BSM physics searches, and reactor flux and spectrum modeling. The community's aims offer strong complimentary with numerous aspects of the wider US neutrino program and have direct relevance to most of the topical sub-groups composing the Snowmass 2021 Neutrino Frontier. Reactor neutrino experiments also have a direct societal impact and have become a strong workforce and technology development pipeline for DOE National Laboratories and universities. This white paper, prepared as a submission to the Snowmass 2021 community organizing exercise, will survey the state of the reactor antineutrino physics field and summarize the ways in which current and future reactor antineutrino experiments can play a critical role in advancing the field of particle physics in the next decade

High Energy Physics Opportunities Using Reactor Antineutrinos

Nuclear reactors are uniquely powerful, abundant, and flavor-pure sources of antineutrinos that continue to play a vital role in the US neutrino physics program. The US reactor antineutrino physics community is a diverse interest group encompassing many detection technologies and many particle physics topics, including Standard Model and short-baseline oscillations, BSM physics searches, and reactor flux and spectrum modeling. The community's aims offer strong complimentary with numerous aspects of the wider US neutrino program and have direct relevance to most of the topical sub-groups composing the Snowmass 2021 Neutrino Frontier. Reactor neutrino experiments also have a direct societal impact and have become a strong workforce and technology development pipeline for DOE National Laboratories and universities. This white paper, prepared as a submission to the Snowmass 2021 community organizing exercise, will survey the state of the reactor antineutrino physics field and summarize the ways in which current and future reactor antineutrino experiments can play a critical role in advancing the field of particle physics in the next decade

High Energy Physics Opportunities Using Reactor Antineutrinos

Nuclear reactors are uniquely powerful, abundant, and flavor-pure sources of antineutrinos that continue to play a vital role in the US neutrino physics program. The US reactor antineutrino physics community is a diverse interest group encompassing many detection technologies and many particle physics topics, including Standard Model and short-baseline oscillations, BSM physics searches, and reactor flux and spectrum modeling. The community's aims offer strong complimentary with numerous aspects of the wider US neutrino program and have direct relevance to most of the topical sub-groups composing the Snowmass 2021 Neutrino Frontier. Reactor neutrino experiments also have a direct societal impact and have become a strong workforce and technology development pipeline for DOE National Laboratories and universities. This white paper, prepared as a submission to the Snowmass 2021 community organizing exercise, will survey the state of the reactor antineutrino physics field and summarize the ways in which current and future reactor antineutrino experiments can play a critical role in advancing the field of particle physics in the next decade

High Energy Physics Opportunities Using Reactor Antineutrinos

Nuclear reactors are uniquely powerful, abundant, and flavor-pure sources of antineutrinos that continue to play a vital role in the US neutrino physics program. The US reactor antineutrino physics community is a diverse interest group encompassing many detection technologies and many particle physics topics, including Standard Model and short-baseline oscillations, BSM physics searches, and reactor flux and spectrum modeling. The community's aims offer strong complimentary with numerous aspects of the wider US neutrino program and have direct relevance to most of the topical sub-groups composing the Snowmass 2021 Neutrino Frontier. Reactor neutrino experiments also have a direct societal impact and have become a strong workforce and technology development pipeline for DOE National Laboratories and universities. This white paper, prepared as a submission to the Snowmass 2021 community organizing exercise, will survey the state of the reactor antineutrino physics field and summarize the ways in which current and future reactor antineutrino experiments can play a critical role in advancing the field of particle physics in the next decade

High Energy Physics Opportunities Using Reactor Antineutrinos

Nuclear reactors are uniquely powerful, abundant, and flavor-pure sources of antineutrinos that continue to play a vital role in the US neutrino physics program. The US reactor antineutrino physics community is a diverse interest group encompassing many detection technologies and many particle physics topics, including Standard Model and short-baseline oscillations, BSM physics searches, and reactor flux and spectrum modeling. The community's aims offer strong complimentary with numerous aspects of the wider US neutrino program and have direct relevance to most of the topical sub-groups composing the Snowmass 2021 Neutrino Frontier. Reactor neutrino experiments also have a direct societal impact and have become a strong workforce and technology development pipeline for DOE National Laboratories and universities. This white paper, prepared as a submission to the Snowmass 2021 community organizing exercise, will survey the state of the reactor antineutrino physics field and summarize the ways in which current and future reactor antineutrino experiments can play a critical role in advancing the field of particle physics in the next decade

High Energy Physics Opportunities Using Reactor Antineutrinos

Nuclear reactors are uniquely powerful, abundant, and flavor-pure sources of antineutrinos that continue to play a vital role in the US neutrino physics program. The US reactor antineutrino physics community is a diverse interest group encompassing many detection technologies and many particle physics topics, including Standard Model and short-baseline oscillations, BSM physics searches, and reactor flux and spectrum modeling. The community's aims offer strong complimentary with numerous aspects of the wider US neutrino program and have direct relevance to most of the topical sub-groups composing the Snowmass 2021 Neutrino Frontier. Reactor neutrino experiments also have a direct societal impact and have become a strong workforce and technology development pipeline for DOE National Laboratories and universities. This white paper, prepared as a submission to the Snowmass 2021 community organizing exercise, will survey the state of the reactor antineutrino physics field and summarize the ways in which current and future reactor antineutrino experiments can play a critical role in advancing the field of particle physics in the next decade