Abstract
The spatial organization of chromatin in the nucleus has been implicated in regulating gene expression. Maps of high-frequency interactions between different segments of chromatin have revealed topologically associating domains (TADs), within which most of the regulatory interactions are thought to occur. TADs are not homogeneous structural units but appear to be organized into a hierarchy. We present OnTAD, an optimized nested TAD caller from Hi-C data, to identify hierarchical TADs. OnTAD reveals new biological insights into the role of different TAD levels, boundary usage in gene regulation, the loop extrusion model, and compartmental domains. OnTAD is available at https://github.com/anlin00007/OnTAD.
Highlights
Previous studies have shown that the human genome is spatially organized at different levels in the nucleus, with each level of organization playing a role in gene regulation [1]
Because the sizes of topologically associating domains” (TADs) are unknown, OnTAD repeats the above steps using a series of window sizes, W = 1, 2., ..., K, to uncover all possible boundaries for TADs in different sizes
Level of TAD hierarchy is related to gene activity and epigenomic states We systematically studied the biological features of the TAD hierarchy, again using the Hi-C data in GM12878 from Rao et al [17]
Summary
Previous studies have shown that the human genome is spatially organized at different levels in the nucleus, with each level of organization playing a role in gene regulation [1]. Starting with the original Chromatin Conformation Capture (3C) assay [2] for measuring chromatin interaction frequencies, many higher throughput, sequencingbased methods such as 4C, 5C, ChIA-PET, Hi-C, and Hi-ChIP have been developed to measure 3D interaction frequencies at different resolutions [3,4,5,6,7,8]. These maps of interaction frequencies between segments of chromatin are interpreted in terms of chromatin structures. The positions of many TADs are similar across different cell types and
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