Oncogenic fusion proteins and their role in three-dimensional chromatin structure, phase separation, and cancer

Quiroga, Ivana Yoseli; Ahn, Jeong Hyun; Wang, Gang Greg; Phanstiel, Douglas H.

doi:10.1016/j.gde.2022.101901

Cited by 17 publications

(21 citation statements)

References 69 publications

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“…Appropriate folding and spatial partitioning of 3D genome were proposed to be crucial for ensuring and/or facilitating a range of DNA-templated biological processes, such as coordinated co-transcription or co-silencing of genes within the same compartments (such as euchromatin and heterochromatin), the orderly genome replication, and genome integrity [ 11 , 13–21 ]. On the other hand, misregulation of 3D chromatin structure has been widely linked to, sometimes found to be causal for, development of diseases [ 22 ], including cancer [ 23–27 ], immunological malfunction [ 28 ], and neurological or developmental syndrome [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the increasing amount of evidence points to critical roles of phase separation in determining and/or shaping the landscape of 3D chromatin structures [ 15 , 19 , 23 , 50–57 ]. In the next section, we will briefly cover the concept of phase separation and its involvements in establishing both higher-order (such as compartmentalization) and fine-scale 3D structures (such as loops).…”

Section: Introductionmentioning

confidence: 99%

“…IDPs refer to proteins enriched in intrinsically disordered regions (IDRs), which exhibit a strong tendency to phase separate [ 58–62 ]. As IDPs/IDRs are frequently associated with pathogenesis [ 23 , 63 ], an improved understanding of IDP-/IDR-associated 3D genome folding may help to develop new therapeutics for the affected patients.…”

Section: Introductionmentioning

confidence: 99%

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Through the lens of phase separation: intrinsically unstructured protein and chromatin looping

Cai

Wang

2023

Nucleus

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The establishment, maintenance and dynamic regulation of three-dimensional (3D) chromatin structures provide an important means for partitioning of genome into functionally distinctive domains, which helps to define specialized gene expression programs associated with developmental stages and cell types. Increasing evidence supports critical roles for intrinsically disordered regions (IDRs) harbored within transcription factors (TFs) and chromatin-modulatory proteins in inducing phase separation, a phenomenon of forming membrane-less condensates through partitioning of biomolecules. Such a process is also critically involved in the establishment of high-order chromatin structures and looping. IDR- and phase separation-driven 3D genome (re)organization often goes wrong in disease such as cancer. This review discusses about recent advances in understanding how phase separation of intrinsically disordered proteins (IDPs) modulates chromatin looping and gene expression.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Through the lens of phase separation: intrinsically unstructured protein and chromatin looping

Cai

Wang

2023

Nucleus

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“…Cancer cells, in addition, display genomic rearrangements that have consequences on three-dimensional (3D) and radial (center-to-periphery) chromatin organization, which are reinforced by epigenetic alterations of DNA and histones. Genomic and 3D chromatin changes resulting from senescence and cancer initiation have been recently reviewed elsewhere (senescence [ 3 , 4 , 5 , 6 ]; cancer [ 7 , 8 , 9 ]) and are not addressed here.…”

Section: Introductionmentioning

confidence: 99%

Restructuring of Lamina-Associated Domains in Senescence and Cancer

Bellanger

Madsen-Østerbye

Galigniana

et al. 2022

Cells

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Induction of cellular senescence or cancer is associated with a reshaping of the nuclear envelope and a broad reorganization of heterochromatin. At the periphery of mammalian nuclei, heterochromatin is stabilized at the nuclear lamina via lamina-associated domains (LADs). Alterations in the composition of the nuclear lamina during senescence lead to a loss of peripheral heterochromatin, repositioning of LADs, and changes in epigenetic states of LADs. Cancer initiation and progression are also accompanied by a massive reprogramming of the epigenome, particularly in domains coinciding with LADs. Here, we review recent knowledge on alterations in chromatin organization and in the epigenome that affect LADs and related genomic domains in senescence and cancer.

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“…Increasing evidence points to critical roles of three-dimensional (3D) chromatin organization and high-order structure during organismal development and cell differentiation, and deregulation of chromatin topology is associated with development of human diseases ( Bonev and Cavalli, 2016 ; Yu and Ren, 2017 ; Hansen et al, 2018 ; Hug and Vaquerizas, 2018 ; Brien and Bracken, 2019 ; Zheng and Xie, 2019 ; Quiroga et al, 2022 ). In recent years, deep sequencing- and imaging-based technologies developed for mapping 3D chromatin structure have shed new light on spatiotemporal organization of 3D chromatin organization and long-range contacts.…”

Section: Introductionmentioning

confidence: 99%

Modulation of the high-order chromatin structure by Polycomb complexes

Guo

Wang²

2022

Front. Cell Dev. Biol.

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The multi-subunit Polycomb Repressive Complex (PRC) 1 and 2 act, either independently or synergistically, to maintain and enforce a repressive state of the target chromatin, thereby regulating the processes of cell lineage specification and organismal development. In recent years, deep sequencing-based and imaging-based technologies, especially those tailored for mapping three-dimensional (3D) chromatin organization and structure, have allowed a better understanding of the PRC complex-mediated long-range chromatin contacts and DNA looping. In this review, we review current advances as for how Polycomb complexes function to modulate and help define the high-order chromatin structure and topology, highlighting the multi-faceted roles of Polycomb proteins in gene and genome regulation.

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Oncogenic fusion proteins and their role in three-dimensional chromatin structure, phase separation, and cancer

Cited by 17 publications

References 69 publications

Through the lens of phase separation: intrinsically unstructured protein and chromatin looping

Through the lens of phase separation: intrinsically unstructured protein and chromatin looping

Restructuring of Lamina-Associated Domains in Senescence and Cancer

Modulation of the high-order chromatin structure by Polycomb complexes

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