한빛사논문
- 조회390
University of California, San Francisco, San Francisco Veterans Affairs Medical Center
Sajad Hamid Ahanger 1,2,3,11, Ryan N. Delgado1,2,4,11, Eugene Gil1,2, Mitchel A. Cole2,5, Jingjing Zhao6,7, Sung Jun Hong1,2,8, Arnold R. Kriegstein 2,9, Tomasz J. Nowakowski2,4,10, Alex A. Pollen2,9 and Daniel A. Lim 1,2,3,*
1Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA. 2Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA. 3San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA. 4Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA. 5Medical Scientist Training Program, Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA. 6Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA. 7Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA. 8Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, San Francisco, CA, USA. 9Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. 10Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA. 11These authors contributed equally: Sajad Hamid Ahanger, Ryan N. Delgado.
*Correspondence to Daniel A. Lim.
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.
논문정보
- Research article
- 2021년 07월 (BRIC 등록일 2021-07-19)
- 국외 연구진
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