Micro-C-TALE: BAC-based targeted high-resolution measurement of 3D chromatin interactions
- 1Technion - Israel Institute of Technology
Abstract
Chromosome conformation capture methods have greatly advanced our understanding of genome organization, but obtaining high-resolution interaction maps of selected genomic regions remains costly due to the sequencing requirements. Here, we introduce Micro-C-TALE, a new chromosome conformation capture method that combines Micro-C, which uses micrococcal nuclease to improve the resolution and sensitivity of chromatin interaction measurements, and C-TALE, which uses probes generated from bacterial artificial chromosomes (BACs) for targeted enrichment. This combination enables the generation of high-resolution interaction maps without requiring custom synthesis of capture oligonucleotides. We applied Micro-C-TALE to a 214 kb region in human HAP1 cells, obtaining detailed interaction maps with approximately 5-6 million sequenced read pairs. Compared with published genome-wide Micro-C data, Micro-C-TALE yielded a higher amount of informative interactions within the targeted region despite ~550-fold lower sequencing depth. To evaluate the sensitivity of the method to fine-scale changes in genome organization, we introduced a heterozygous CTCF binding site into the targeted region using CRISPR-Cas9. Comparing Micro-C-TALE to the restriction enzyme-based C-TALE, we found Micro-C-TALE yielded a ~5-fold higher fraction of informative reads and detected novel CTCF-mediated point interactions associated with the inserted CTCF site, which were barely discernible using C-TALE. Our results demonstrate that Micro-C-TALE provides a flexible and cost-effective approach for targeted high-resolution measurement of chromatin interactions, facilitating the investigation of fine-scale genome organization and its response to genetic perturbations.
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BibTeX
@misc{golberg2026microctale,
title = {{Micro-C-TALE: BAC-based targeted high-resolution measurement of 3D chromatin interactions}},
author = {A. Golberg and A. K. Golov and R. Shemer and N. Kaplan},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.21.760768},
url = {https://www.biorxiv.org/content/10.64898/2026.10.21.760768v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Micro-C-TALE: BAC-based targeted high-resolution measurement of 3D chromatin interactions
AU - A. Golberg
AU - A. K. Golov
AU - R. Shemer
AU - N. Kaplan
PY - 2026
DA - 2026/10/21
PB - bioRxiv
DO - 10.64898/2026.10.21.760768
UR - https://www.biorxiv.org/content/10.64898/2026.10.21.760768v1
AB - Chromosome conformation capture methods have greatly advanced our understanding of genome organization, but obtaining high-resolution interaction maps of selected genomic regions remains costly due to the sequencing requirements. Here, we introduce Micro-C-TALE, a new chromosome conformation capture method that combines Micro-C, which uses micrococcal nuclease to improve the resolution and sensitivity of chromatin interaction measurements, and C-TALE, which uses probes generated from bacterial artificial chromosomes (BACs) for targeted enrichment. This combination enables the generation of high-resolution interaction maps without requiring custom synthesis of capture oligonucleotides. We applied Micro-C-TALE to a 214 kb region in human HAP1 cells, obtaining detailed interaction maps with approximately 5-6 million sequenced read pairs. Compared with published genome-wide Micro-C data, Micro-C-TALE yielded a higher amount of informative interactions within the targeted region despite ~550-fold lower sequencing depth. To evaluate the sensitivity of the method to fine-scale changes in genome organization, we introduced a heterozygous CTCF binding site into the targeted region using CRISPR-Cas9. Comparing Micro-C-TALE to the restriction enzyme-based C-TALE, we found Micro-C-TALE yielded a ~5-fold higher fraction of informative reads and detected novel CTCF-mediated point interactions associated with the inserted CTCF site, which were barely discernible using C-TALE. Our results demonstrate that Micro-C-TALE provides a flexible and cost-effective approach for targeted high-resolution measurement of chromatin interactions, facilitating the investigation of fine-scale genome organization and its response to genetic perturbations.
ER -