Distinct nuclear compartment-associated genome architecture in the developing mammalian brain. Ahanger, S. H., Delgado, R. N, Gil, E., Cole, M. A, Zhao, J., Hong, S. J., Kriegstein, A. R, Nowakowski, T. J, Pollen, A. A, & Lim, D. A Nat Neurosci, 24(9):1235–1242, July, 2021. abstract bibtex Nuclear compartments are thought to play a role in three-dimensional genome organization and gene expression. In mammalian brain, the architecture and dynamics of nuclear compartment-associated genome organization is not known. In this study, we developed Genome Organization using CUT and RUN Technology (GO-CaRT) to map genomic interactions with two nuclear compartments-the nuclear lamina and nuclear speckles-from different regions of the developing mouse, macaque and human brain. Lamina-associated domain (LAD) architecture in cells in vivo is distinct from that of cultured cells, including major differences in LADs previously considered to be cell type invariant. In the mouse and human forebrain, dorsal and ventral neural precursor cells have differences in LAD architecture that correspond to their regional identity. LADs in the human and mouse cortex contain transcriptionally highly active sub-domains characterized by broad depletion of histone-3-lysine-9 dimethylation. Evolutionarily conserved LADs in human, macaque and mouse brain are enriched for transcriptionally active neural genes associated with synapse function. By integrating GO-CaRT maps with genome-wide association study data, we found speckle-associated domains to be enriched for schizophrenia risk loci, indicating a physical relationship between these disease-associated genetic variants and a specific nuclear structure. Our work provides a framework for understanding the relationship between distinct nuclear compartments and genome function in brain development and disease.
@ARTICLE{Ahanger2021-ke,
title = "Distinct nuclear compartment-associated genome architecture in
the developing mammalian brain",
author = "Ahanger, Sajad Hamid and Delgado, Ryan N and Gil, Eugene and
Cole, Mitchel A and Zhao, Jingjing and Hong, Sung Jun and
Kriegstein, Arnold R and Nowakowski, Tomasz J and Pollen, Alex A
and Lim, Daniel A",
abstract = "Nuclear compartments are thought to play a role in
three-dimensional genome organization and gene expression. In
mammalian brain, the architecture and dynamics of nuclear
compartment-associated genome organization is not known. In this
study, we developed Genome Organization using CUT and RUN
Technology (GO-CaRT) to map genomic interactions with two nuclear
compartments-the nuclear lamina and nuclear speckles-from
different regions of the developing mouse, macaque and human
brain. Lamina-associated domain (LAD) architecture in cells in
vivo is distinct from that of cultured cells, including major
differences in LADs previously considered to be cell type
invariant. In the mouse and human forebrain, dorsal and ventral
neural precursor cells have differences in LAD architecture that
correspond to their regional identity. LADs in the human and
mouse cortex contain transcriptionally highly active sub-domains
characterized by broad depletion of histone-3-lysine-9
dimethylation. Evolutionarily conserved LADs in human, macaque
and mouse brain are enriched for transcriptionally active neural
genes associated with synapse function. By integrating GO-CaRT
maps with genome-wide association study data, we found
speckle-associated domains to be enriched for schizophrenia risk
loci, indicating a physical relationship between these
disease-associated genetic variants and a specific nuclear
structure. Our work provides a framework for understanding the
relationship between distinct nuclear compartments and genome
function in brain development and disease.",
journal = "Nat Neurosci",
volume = 24,
number = 9,
pages = "1235--1242",
month = jul,
year = 2021,
language = "en"
}
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A"],"bibdata":{"bibtype":"article","type":"article","title":"Distinct nuclear compartment-associated genome architecture in the developing mammalian brain","author":[{"propositions":[],"lastnames":["Ahanger"],"firstnames":["Sajad","Hamid"],"suffixes":[]},{"propositions":[],"lastnames":["Delgado"],"firstnames":["Ryan","N"],"suffixes":[]},{"propositions":[],"lastnames":["Gil"],"firstnames":["Eugene"],"suffixes":[]},{"propositions":[],"lastnames":["Cole"],"firstnames":["Mitchel","A"],"suffixes":[]},{"propositions":[],"lastnames":["Zhao"],"firstnames":["Jingjing"],"suffixes":[]},{"propositions":[],"lastnames":["Hong"],"firstnames":["Sung","Jun"],"suffixes":[]},{"propositions":[],"lastnames":["Kriegstein"],"firstnames":["Arnold","R"],"suffixes":[]},{"propositions":[],"lastnames":["Nowakowski"],"firstnames":["Tomasz","J"],"suffixes":[]},{"propositions":[],"lastnames":["Pollen"],"firstnames":["Alex","A"],"suffixes":[]},{"propositions":[],"lastnames":["Lim"],"firstnames":["Daniel","A"],"suffixes":[]}],"abstract":"Nuclear compartments are thought to play a role in three-dimensional genome organization and gene expression. In mammalian brain, the architecture and dynamics of nuclear compartment-associated genome organization is not known. In this study, we developed Genome Organization using CUT and RUN Technology (GO-CaRT) to map genomic interactions with two nuclear compartments-the nuclear lamina and nuclear speckles-from different regions of the developing mouse, macaque and human brain. Lamina-associated domain (LAD) architecture in cells in vivo is distinct from that of cultured cells, including major differences in LADs previously considered to be cell type invariant. In the mouse and human forebrain, dorsal and ventral neural precursor cells have differences in LAD architecture that correspond to their regional identity. LADs in the human and mouse cortex contain transcriptionally highly active sub-domains characterized by broad depletion of histone-3-lysine-9 dimethylation. Evolutionarily conserved LADs in human, macaque and mouse brain are enriched for transcriptionally active neural genes associated with synapse function. By integrating GO-CaRT maps with genome-wide association study data, we found speckle-associated domains to be enriched for schizophrenia risk loci, indicating a physical relationship between these disease-associated genetic variants and a specific nuclear structure. 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In this\n study, we developed Genome Organization using CUT and RUN\n Technology (GO-CaRT) to map genomic interactions with two nuclear\n compartments-the nuclear lamina and nuclear speckles-from\n different regions of the developing mouse, macaque and human\n brain. Lamina-associated domain (LAD) architecture in cells in\n vivo is distinct from that of cultured cells, including major\n differences in LADs previously considered to be cell type\n invariant. In the mouse and human forebrain, dorsal and ventral\n neural precursor cells have differences in LAD architecture that\n correspond to their regional identity. LADs in the human and\n mouse cortex contain transcriptionally highly active sub-domains\n characterized by broad depletion of histone-3-lysine-9\n dimethylation. Evolutionarily conserved LADs in human, macaque\n and mouse brain are enriched for transcriptionally active neural\n genes associated with synapse function. By integrating GO-CaRT\n maps with genome-wide association study data, we found\n speckle-associated domains to be enriched for schizophrenia risk\n loci, indicating a physical relationship between these\n disease-associated genetic variants and a specific nuclear\n structure. Our work provides a framework for understanding the\n relationship between distinct nuclear compartments and genome\n function in brain development and disease.\",\n journal = \"Nat Neurosci\",\n volume = 24,\n number = 9,\n pages = \"1235--1242\",\n month = jul,\n year = 2021,\n language = \"en\"\n}\n\n","author_short":["Ahanger, S. H.","Delgado, R. N","Gil, E.","Cole, M. A","Zhao, J.","Hong, S. J.","Kriegstein, A. R","Nowakowski, T. J","Pollen, A. A","Lim, D. 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