Browsing by Author "He, C."
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Item Long Genes Linked to Autism Spectrum Disorders Harbor Broad Enhancer-Like Chromatin Domains(Cold Spring Harbor Laboratory Press) Zhao, Y. -T; Kwon, D. Y.; Johnson, B. S.; Fasolino, M.; Lamonica, J. M.; Kim, Yoon Jung; Zhao, B. S.; He, C.; Vahedi, G.; Kim, Tae Hoon; Zhou, Z.; Kim, Yoon Jung; Kim, Tae HoonGenetic 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 alternations in ASD-associated chromatin regulators. These findings suggest that the epigenomic regulation of BELD genes is important for post-natal cortical development and lend support to a model by which mutations in chromatin regulators causally contribute to ASDs by preferentially impairing BELD gene transcription.Item Nucleosome Eviction and Multiple Co-Factor Binding Predict Estrogen-Receptor-Alpha-Asociated Long-Range Interactions(Oxford University Press, 2014-04-29) He, C.; Wang, X.; Zhang, Michael Q.; 0000 0001 1707 1372 (Zhang, MQ); 99086074 (Zhang, MQ); Zhang, Michael Q.Many enhancers regulate their target genes via long-distance interactions. High-throughput experiments like ChIA-PET have been developed to map such largely cell-type-specific interactions between cis-regulatory elements genome-widely. In this study, we integrated multiple types of data in order to reveal the general hidden patterns embedded in the ChIA-PET data. We found characteristic distance features related to promoter-promoter, enhancer-enhancer and insulator-insulator interactions. Although a protein may have many binding sites along the genome, our hypothesis is that those sites that share certain open chromatin structure can accommodate relatively larger protein complex consisting of specific regulatory and 'bridging' factors, and may be more likely to form robust long-range deoxyribonucleic acid (DNA) loops. This hypothesis was validated in the estrogen receptor alpha (ERa) ChIA-PET data. An efficient classifier was built to predict ERa-associated long-range interactions solely from the related ChIP-seq data, hence linking distal ERa-dependent enhancers to their target genes. We further applied the classifier to generate additional novel interactions, which were undetected in the original ChIA-PET paper but were validated by other independent experiments. Our work provides a new insight into the long-range chromatin interactions through deeper and integrative ChIA-PET data analysis and demonstrates DNA looping predictability from ordinary ChIP-seq data.