CSB Research
Permanent URI for this collectionhttps://hdl.handle.net/10735.1/3686
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Browsing CSB Research by Author "99086074 (Zhang, MQ)"
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Item Distinct and Predictive Histone Lysine Acetylation Patterns at Promoters, Enhancers, and Gene Bodies(Genetics Society America, 2014-11-01) Rajagopal, Nisha; Ernst, Jason; Ray, Pradipta; Wu, Jie; Zhang, Michael Q.; Kellis, Manolis; Ren, Bing; 0000 0001 1707 1372 (Zhang, MQ); 99086074 (Zhang, MQ); Zhang, Michael Q.In eukaryotic cells, histone lysines are frequently acetylated. However, unlike modifications such as methylations, histone acetylation modifications are often considered redundant. As such, the functional roles of distinct histone acetylations are largely unexplored. We previously developed an algorithm RFECS to discover the most informative modifications associated with the classification or prediction of mammalian enhancers. Here, we used this tool to identify the modifications most predictive of promoters, enhancers, and gene bodies. Unexpectedly, we found that histone acetylation alone performs well in distinguishing these unique genomic regions. Further, we found the association of characteristic acetylation patterns with genic regions and association of chromatin state with splicing. Taken together, our work underscores the diverse functional roles of histone acetylation in gene regulation and provides several testable hypotheses to dissect these roles.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.