Abstract
Recent chromosome conformation capture (3C) derived techniques have revealed that topologically associating domain (TAD) is a pervasive element in chromatin three-dimensional (3D) organization. However, there is currently no parameter to quantitatively measure the structural characteristics of TADs, thus obscuring our understanding on the structural and functional differences among TADs. Based on our finding that there exist intrinsic chromatin interaction patterns in TADs, we define a theoretical parameter, called aggregation preference (AP), to characterize TAD structures by capturing the interaction aggregation degree. Applying this defined parameter to 11 Hi-C data sets generated by both traditional and in situ Hi-C experimental pipelines, our analyses reveal that heterogeneous structures exist among TADs, and this structural heterogeneity is significantly correlated to DNA sequences, epigenomic signals and gene expressions. Although TADs can be stable in genomic positions across cell lines, structural comparisons show that a considerable number of stable TADs undergo significantly structural rearrangements during cell changes. Moreover, the structural change of TAD is tightly associated with its transcription remodeling. Altogether, the theoretical parameter defined in this work provides a quantitative method to link structural characteristics and biological functions of TADs, and this linkage implies that chromatin interaction pattern has the potential to mark transcription activity in TADs.
Highlights
Recent chromosome conformation capture (3C) derived techniques [1,2], especially Hi-C [3], have revealed that chromatins are partitioned into topologically associating domains (TADs), called topological domains, in which the intra-domain chromatin interactions are significantly stronger than inter-domain interactions
Five traditional Hi-C maps are denoted as hESC-T, GM12878-T, IMR90-T, mESC-T and Cortex-T to represent three human cell lines and two mouse cell lines, while six in situ Hi-C maps are denoted as GM12878-I, IMR90I, K562-I, HMEC-I, HUVEC-I and NHEK-I to represent corresponding human cell lines
Since different kinds of structural characteristics can be obtained at different resolutions due to hierarchical chromatin architecture [27], the TADs identified from different resolutions are not directly compared in this work
Summary
Recent chromosome conformation capture (3C) derived techniques [1,2], especially Hi-C [3], have revealed that chromatins are partitioned into topologically associating domains (TADs), called topological domains, in which the intra-domain chromatin interactions are significantly stronger than inter-domain interactions. TAD acts as a pervasive, or at least in part, structural element of chromatin three-dimensional (3D) organization across species, including Caulobacter crescentus [4], Plasmodium falciparum [5], Arabidopsis [6,7], yeast [8], drosophila [9], mouse [10,11] and human [11]. TAD provides structural basis for chromatin regulation. The study on mouse revealed that the limb development was regulated by the switch of two neighbor TADs [13]. A recent work on bacteria C. crescentus provided the direct evidence that disrupting TADs leads to the change of gene expressions [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
