![]() Many nonvertebrate organisms, including Caenorhabditis elegans, lack a CTCF homolog ( Heger et al. Instead, Drosophila contact maps in Kc167 cells contain a few hundred loops that lack CTCF, and their formation does not depend on cohesin ( Rowley et al. For example, Drosophila Hi-C maps do not display CTCF loops despite the existence of a conserved Drosophila homolog ( Rowley et al. 2014).ĬTCF loops have been identified in mammals but have not been observed in other organisms. However, other transcription factors are also present at CTCF loop anchors, and it is unclear whether or not they play a role in loop extrusion or affect the frequency or stability of CTCF loops ( Rao et al. Indeed, depletion of cohesin in mammalian cells results in loss of CTCF loops ( Rao et al. Based on this orientation preference, it has been proposed that CTCF loops are formed by a loop extrusion process mediated by cohesin (for review, see Rowley and Corces 2018). High resolution Hi-C in human cells is able to find thousands of strong punctate signals that indicate the presence of loops formed by CTCF sites arranged in a convergent orientation ( Rao et al. 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. This is in contrast to the asymmetrical extrusion until unidirectional blockage by CTCF that is presumed to occur in mammals. 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. 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. SIPMeta corrects for a common visualization artifact by accounting for Manhattan distance to create average plots of Hi-C and HiChIP data. 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. 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. 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. ![]() Identification of these loops is a critical part of most Hi-C analyses. Chromatin loops are a major component of 3D nuclear organization, visually apparent as intense point-to-point interactions in Hi-C maps.
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