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This study demonstrates the dependence of non-local susceptibility effects on object orientation in gradient echo MRI and the reduction of non-local effects by deconvolution using quantitative susceptibility mapping (QSM). Imaging experiments were performed on a 3T MRI system using a spoiled 3D multi-echo GRE sequence on phantoms of known susceptibilities, and on human brains of healthy subjects and patients with intracerebral hemorrhages. Magnetic field measurements were determined from multiple echo phase data. To determine the QSM, these field measurements were deconvolved through a dipole inversion kernel under a constraint of consistency with the magnitude images. Phantom and human data demonstrated that the hypointense region in GRE magnitude image corresponding to a susceptibility source increased in volume with TE and varied with the source orientation. The induced magnetic field extended beyond the susceptibility source and varied with its orientation. In QSM, these blooming artifacts, including their dependence on object orientation, were reduced and material susceptibilities were quantified.

Eukaryotic chromosomes are folded into higher-order conformations to coordinate genome functions. In addition to long-range chromatin loops, recent chromosome conformation capture (3C)-based studies have indicated higher levels of chromatin structures including compartments and topologically associating domains (TADs), which may serve as units of genome organization and functions. However, the molecular machinery underlying these hierarchically three-dimensional (3D) chromatin architectures remains poorly understood. Via high-throughput assays, including in situ Hi-C, DamID, ChIP-seq, and RNA-seq, we investigated roles of the Heterogeneous Nuclear Ribonucleoprotein U (HNRNPU), a nuclear matrix (NM)-associated protein, in 3D genome organization. Upon the depletion of HNRNPU in mouse hepatocytes, the coverage of lamina-associated domains (LADs) in the genome increases from 53.1% to 68.6%, and a global condensation of chromatin was observed. Furthermore, disruption of HNRNPU leads to compartment switching on 7.5% of the genome, decreases TAD boundary strengths at borders between A (active) and B (inactive) compartments, and reduces chromatin loop intensities. Long-range chromatin interactions between and within compartments or TADs are also significantly remodeled upon HNRNPU depletion. Intriguingly, HNRNPU mainly associates with active chromatin, and 80% of HNRNPU peaks coincide with the binding of CTCF or RAD21. Collectively, we demonstrated that HNRNPU functions as a major factor maintaining 3D chromatin architecture, suggesting important roles of NM-associated proteins in genome organization.

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Highlights d SAFB maintains higher-order organization of pericentromeric heterochromatin d SAFB interacts with repeat element RNAs such as MajSAT d SAFB drives phase separation that is promoted by MajSAT RNAs d Depletion of SAFB leads to a remodeling of 3D genome organization