Analysis of Hi-C data using SIP effectively identifies loops in organisms from C. elegans to mammals
- M. Jordan Rowley1,6,7,
- Axel Poulet1,6,8,
- Michael H. Nichols2,
- Brianna J. Bixler2,
- Adrian L. Sanborn3,
- Elizabeth A. Brouhard4,
- Karen Hermetz2,
- Hannah Linsenbaum2,
- Gyorgyi Csankovszki4,
- Erez Lieberman Aiden3,5 and
- Victor G. Corces2
- 1Department of Biology, Emory University, Atlanta, Georgia 30322, USA;
- 2Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA;
- 3Center for Genome Architecture, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA;
- 4Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 5Center for Theoretical Biological Physics and Department of Computer Science, Rice University, Houston, Texas 77005, USA
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↵6 These authors contributed equally to this work.
Abstract
Chromatin loops are a major component of 3D nuclear organization, visually apparent as intense point-to-point interactions in Hi-C maps. Identification of these loops is a critical part of most Hi-C analyses. However, current methods often miss visually evident CTCF loops in Hi-C data sets from mammals, and they completely fail to identify high intensity loops in other organisms. We present SIP, Significant Interaction Peak caller, and SIPMeta, which are platform independent programs to identify and characterize these loops in a time- and memory-efficient manner. We show that SIP is resistant to noise and sequencing depth, and can be used to detect loops that were previously missed in human cells as well as loops in other organisms. SIPMeta corrects for a common visualization artifact by accounting for Manhattan distance to create average plots of Hi-C and HiChIP data. We then demonstrate that the use of SIP and SIPMeta can lead to biological insights by characterizing the contribution of several transcription factors to CTCF loop stability in human cells. We also annotate loops associated with the SMC component of the dosage compensation complex (DCC) in Caenorhabditis elegans and demonstrate that loop anchors represent bidirectional blocks for symmetrical loop extrusion. This is in contrast to the asymmetrical extrusion until unidirectional blockage by CTCF that is presumed to occur in mammals. Using HiChIP and multiway ligation events, we then show that DCC loops form a network of strong interactions that may contribute to X Chromosome–wide condensation in C. elegans hermaphrodites.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.257832.119.
- Received October 1, 2019.
- Accepted February 25, 2020.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
