TY - JOUR
T1 - Spatial genome exploration in the context of cognitive and neurological disease
AU - Rajarajan, Prashanth
AU - Borrman, Tyler
AU - Liao, Will
AU - Espeso-Gil, Sergio
AU - Chandrasekaran, Sandhya
AU - Jiang, Yan
AU - Weng, Zhiping
AU - Brennand, Kristen J.
AU - Akbarian, Schahram
N1 - Funding Information:
Work conducted in the authors’ laboratories is supported by N.I.H. grants R01MH106056 and R01MH117790.
Funding Information:
Work conducted in the authors’ laboratories is supported by N.I.H. grants R01MH106056 and R01MH117790 .
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/12
Y1 - 2019/12
N2 - The ‘non-linear’ genome, or the spatial proximity of non-contiguous sequences, emerges as an important regulatory layer for genome organization and function, including transcriptional regulation. Here, we review recent genome-scale chromosome conformation mappings (‘Hi-C’) in developing and adult human and mouse brain. Neural differentiation is associated with widespread remodeling of the chromosomal contact map, reflecting dynamic changes in cell-type-specific gene expression programs, with a massive (estimated 20–50%) net loss of chromosomal contacts that is specific for the neuronal lineage. Hi-C datasets provided an unexpected link between locus-specific abnormal expansion of repeat sequences positioned at the boundaries of self-associating topological chromatin domains, and monogenic neurodevelopmental and neurodegenerative disease. Furthermore, integrative cell-type-specific Hi-C and transcriptomic analysis uncovered an expanded genomic risk space for sequences conferring liability for schizophrenia and other cognitive disease. We predict that spatial genome exploration will deliver radically new insights into the brain nucleome in health and disease.
AB - The ‘non-linear’ genome, or the spatial proximity of non-contiguous sequences, emerges as an important regulatory layer for genome organization and function, including transcriptional regulation. Here, we review recent genome-scale chromosome conformation mappings (‘Hi-C’) in developing and adult human and mouse brain. Neural differentiation is associated with widespread remodeling of the chromosomal contact map, reflecting dynamic changes in cell-type-specific gene expression programs, with a massive (estimated 20–50%) net loss of chromosomal contacts that is specific for the neuronal lineage. Hi-C datasets provided an unexpected link between locus-specific abnormal expansion of repeat sequences positioned at the boundaries of self-associating topological chromatin domains, and monogenic neurodevelopmental and neurodegenerative disease. Furthermore, integrative cell-type-specific Hi-C and transcriptomic analysis uncovered an expanded genomic risk space for sequences conferring liability for schizophrenia and other cognitive disease. We predict that spatial genome exploration will deliver radically new insights into the brain nucleome in health and disease.
UR - http://www.scopus.com/inward/record.url?scp=85067862132&partnerID=8YFLogxK
U2 - 10.1016/j.conb.2019.05.007
DO - 10.1016/j.conb.2019.05.007
M3 - Review article
C2 - 31255842
AN - SCOPUS:85067862132
SN - 0959-4388
VL - 59
SP - 112
EP - 119
JO - Current Opinion in Neurobiology
JF - Current Opinion in Neurobiology
ER -