Long genes linked to autism spectrum disorders harbor broad enhancer-like chromatin domains

Genome Research
Ying-Tao ZhaoZhaolan Zhou

Abstract

Genetic variants associated with autism spectrum disorders (ASDs) are enriched in genes encoding synaptic proteins and chromatin regulators. Although the role of synaptic proteins in ASDs is widely studied, the mechanism by which chromatin regulators contribute to ASD risk remains poorly understood. Upon profiling and analyzing the transcriptional and epigenomic features of genes expressed in the cortex, we uncovered a unique set of long genes that contain broad enhancer-like chromatin domains (BELDs) spanning across their entire gene bodies. Analyses of these BELD genes show that they are highly transcribed with frequent RNA polymerase II (Pol II) initiation and low Pol II pausing, and they exhibit frequent chromatin-chromatin interactions within their gene bodies. These BELD features are conserved from rodents to humans, are enriched in genes involved in synaptic function, and appear post-natally concomitant with synapse development. Importantly, we find that BELD genes are highly implicated in neurodevelopmental disorders, particularly ASDs, and that their expression is preferentially down-regulated in individuals with idiopathic autism. Finally, we find that the transcription of BELD genes is particularly sensitive to alter...Continue Reading

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Citations

Dec 7, 2019·The Journal of Biological Chemistry·H Karimi KinyamuTrevor K Archer
Jan 31, 2020·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Giorgi LobzhanidzeMzia Zhvania
Jul 20, 2019·Current Opinion in Genetics & Development·Janine M Lamonica, Zhaolan Zhou
Jan 29, 2022·PloS One·Sohyun Moon, Ying-Tao Zhao

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