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"
}

Downloads: 0