Mitchel A. Cole

Abstract The nuclear genome is spatially organized into a three-dimensional architecture by physical association of large chromosomal domains with subnuclear compartments including the nuclear lamina at the radial periphery and nuclear speckles within the nucleoplasm1,2,3,4,5. However, how higher-order spatial genome architecture regulates human development has been overlooked, and the interplay between chromatin state and subnuclear genome compartmentalization is poorly understood.

Abstract Known fetal hemoglobin (HbF) silencers have potential on-target liabilities for rational β-hemoglobinopathy therapeutic inhibition. Here, through transcription factor (TF) CRISPR screening, we identify zinc-finger protein (ZNF) 410 as an HbF repressor. ZNF410 does not bind directly to the genes encoding γ-globins, but rather its chromatin occupancy is concentrated solely at CHD4, encoding the NuRD nucleosome remodeler, which is itself required for HbF repression.

Access optionsAccess options Subscribe to Journal Get full journal access for 1 year $242.00 only $20.17 per issue All prices are NET prices. VAT will be added later in the checkout. Rent or Buy article Get time limited or full article access on ReadCube. from$8.99 All prices are NET prices. Data availability The data are available at SRA under project number PRJNA494935. References 1. Canver, M. C. et al. Nature 527, 192–197 (2015). 2. Fulco, C. P. et al. Science 354, 769–773 (2016). 3. Simeonov, D. R. et al.