Document Type

Article

Publication Date

5-20-2022

Publication Title

Sci Rep

Keywords

JGM, Chromatin, Chromatin Immunoprecipitation Sequencing, Chromosomes, Genome, Humans, Microscopy

JAX Source

Sci Rep 2022 May 20; 12(1):8582

Volume

12

Issue

1

First Page

8582

Last Page

8582

ISSN

2045-2322

PMID

35595799

DOI

https://doi.org/10.1038/s41598-022-12568-9

Abstract

The three-dimensional (3D) genome structure plays a fundamental role in gene regulation and cellular functions. Recent studies in 3D genomics inferred the very basic functional chromatin folding structures known as chromatin loops, the long-range chromatin interactions that are mediated by protein factors and dynamically extruded by cohesin. We combined the use of FISH staining of a very short (33 kb) chromatin fragment, interferometric photoactivated localization microscopy (iPALM), and traveling salesman problem-based heuristic loop reconstruction algorithm from an image of the one of the strongest CTCF-mediated chromatin loops in human lymphoblastoid cells. In total, we have generated thirteen good quality images of the target chromatin region with 2-22 nm oligo probe localization precision. We visualized the shape of the single chromatin loops with unprecedented genomic resolution which allowed us to study the structural heterogeneity of chromatin looping. We were able to compare the physical distance maps from all reconstructed image-driven computational models with contact frequencies observed by ChIA-PET and Hi-C genomic-driven methods to examine the concordance between single cell imaging and population based genomic data.

Comments

This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0

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