HiChew: a Tool for TAD Clustering in Embryogenesis

The three-dimensional structure of the Drosophila chromatin has been shown to change at the early stages of embryogenesis from the state with no local structures to compartmentalized chromatin segregated into topologically associated domains (TADs). However, the dynamics of TAD formation and its association with the expression and epigenetics dynamics is not fully understood. As TAD calling and analysis of TAD dynamics have no standard, universally accepted solution, we have developed HiChew, a specialized tool for segmentation of Hi-C maps into TADs of a given expected size and subsequent clustering of TADs based on their dynamics during the embryogenesis. To validate the approach, we demonstrate that HiChew clusters correlate with genomic and epigenetic characteristics. Particularly, in accordance with previous findings, the maturation rate of TADs is positively correlated with the number of housekeeping genes per TAD and negatively correlated with the length of housekeeping genes. We also report a high positive correlation of the maturation rate of TADs with the growth rate of the associated ATAC-Seq signal.

[1]  Nezar Abdennur,et al.  Cooler: scalable storage for Hi-C data and other genomically labeled arrays , 2020, Bioinform..

[2]  Melissa M. Harrison,et al.  Mechanisms regulating zygotic genome activation , 2018, Nature Reviews Genetics.

[3]  L. Mirny,et al.  Iterative Correction of Hi-C Data Reveals Hallmarks of Chromosome Organization , 2012, Nature Methods.

[4]  Javier Quilez,et al.  Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming , 2017, Nature Genetics.

[5]  Ulrik Brandes,et al.  On Finding Graph Clusterings with Maximum Modularity , 2007, WG.

[6]  Eric F. Wieschaus,et al.  Zygotic Genome Activation Triggers the DNA Replication Checkpoint at the Midblastula Transition , 2015, Cell.

[7]  Ilya M. Flyamer,et al.  Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains , 2016, Genome research.

[8]  S. Bicciato,et al.  Comparison of computational methods for Hi-C data analysis , 2017, Nature Methods.

[9]  Carl Kingsford,et al.  Analysis of the structural variability of topologically associated domains as revealed by Hi-C , 2019, NAR genomics and bioinformatics.

[10]  Ilya M. Flyamer,et al.  Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition , 2017, Nature.

[11]  A. Tanay,et al.  Multiscale 3D Genome Rewiring during Mouse Neural Development , 2017, Cell.

[12]  Alex T. Kalinka,et al.  The earliest transcribed zygotic genes are short, newly evolved, and different across species. , 2014, Cell reports.

[13]  Neva C. Durand,et al.  Activity-by-Contact model of enhancer-promoter regulation from thousands of CRISPR perturbations , 2019, Nature Genetics.

[14]  Juan M. Vaquerizas,et al.  Chromatin Architecture Emerges during Zygotic Genome Activation Independent of Transcription , 2017, Cell.

[15]  Howard Y. Chang,et al.  Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position , 2013, Nature Methods.