TY - JOUR
AU - Chengyu Deng
AU - Sean Whalen
AU - Marilyn Steyert
AU - Ryan Ziffra
AU - Pawel F. Przytycki
AU - Fumitaka Inoue
AU - Daniela A. Pereira
AU - Davide Capauto
AU - Scott Norton
AU - Flora M. Vaccarino
AU - PsychENCODE Consortium
AU - Alex A. Pollen
AU - Tomasz J. Nowakowski
AU - Nadav Ahituv
AU - Katherine S. Pollard
AB - Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases. Using massively parallel reporter assays in primary human cells from mid-gestation cortex and cerebral organoids, we interrogated the cis-regulatory activity of 102,767 open chromatin regions, including thousands of sequences with cell type–specific accessibility and variants associated with brain gene regulation. In primary cells, we identified 46,802 active enhancer sequences and 164 variants that alter enhancer activity. Activity was comparable in organoids and primary cells, suggesting that organoids provide an adequate model for the developing cortex. Using deep learning we decoded the sequence basis and upstream regulators of enhancer activity. This work establishes a comprehensive catalog of functional gene regulatory elements and variants in human neuronal development.
BT - Science
DA - 2024-05-24
DO - 10.1126/science.adh0559
IS - 6698
N2 - Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases. Using massively parallel reporter assays in primary human cells from mid-gestation cortex and cerebral organoids, we interrogated the cis-regulatory activity of 102,767 open chromatin regions, including thousands of sequences with cell type–specific accessibility and variants associated with brain gene regulation. In primary cells, we identified 46,802 active enhancer sequences and 164 variants that alter enhancer activity. Activity was comparable in organoids and primary cells, suggesting that organoids provide an adequate model for the developing cortex. Using deep learning we decoded the sequence basis and upstream regulators of enhancer activity. This work establishes a comprehensive catalog of functional gene regulatory elements and variants in human neuronal development.
PY - 2024
EP - eadh0559
T2 - Science
TI - Massively parallel characterization of regulatory elements in the developing human cortex
UR - https://www.science.org/doi/10.1126/science.adh0559
VL - 384
Y2 - 2024-06-18
ER -