The 3D Genome: From Structure to Function

Mohanta, Tapan Kumar; Mishra, Awdhesh Kumar; Al‐Harrasi, Ahmed

doi:10.3390/ijms222111585

Cited by 20 publications

(15 citation statements)

References 296 publications

(433 reference statements)

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“…The three‐dimensional (3D) genome structure plays a crucial role in determining cell fate and maintaining normal cellular functions 1 . In the late 19th century, the existence of chromatin territory and euchromatin/heterochromatin in the cell nucleus was proposed based on findings from optical microscopes and chromatin dyes, 2 and Hans Winker introduced the term “genome” in 1920 3 . With the development of fluorescent in situ hybridization, the individual chromosomal territories could be directly observed 4,5 .…”

Section: Introductionmentioning

confidence: 99%

Three‐dimensional genome structure and function

Líu

Tsai

Yang

et al. 2023

MedComm

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Linear DNA undergoes a series of compression and folding events, forming various three‐dimensional (3D) structural units in mammalian cells, including chromosomal territory, compartment, topologically associating domain, and chromatin loop. These structures play crucial roles in regulating gene expression, cell differentiation, and disease progression. Deciphering the principles underlying 3D genome folding and the molecular mechanisms governing cell fate determination remains a challenge. With advancements in high‐throughput sequencing and imaging techniques, the hierarchical organization and functional roles of higher‐order chromatin structures have been gradually illuminated. This review systematically discussed the structural hierarchy of the 3D genome, the effects and mechanisms of cis‐regulatory elements interaction in the 3D genome for regulating spatiotemporally specific gene expression, the roles and mechanisms of dynamic changes in 3D chromatin conformation during embryonic development, and the pathological mechanisms of diseases such as congenital developmental abnormalities and cancer, which are attributed to alterations in 3D genome organization and aberrations in key structural proteins. Finally, prospects were made for the research about 3D genome structure, function, and genetic intervention, and the roles in disease development, prevention, and treatment, which may offer some clues for precise diagnosis and treatment of related diseases.

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Section: Introductionmentioning

confidence: 99%

Three‐dimensional genome structure and function

Líu

Tsai

Yang

et al. 2023

MedComm

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“…The mutant lamins that did not alter nuclear mechanics might play a role in gene expression. Genomes are rich with lamin-associated domains (LADs) in which sections of chromosomes are in close opposition with the lamin meshwork ( Mohanta et al, 2021 ; Wong et al, 2021 ). In fact, in some cell types, LADs represent up to half of the genome ( Briand & Collas, 2020 ; Mohanta et al, 2021 ; Rullens & Kind, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Genomes are rich with lamin-associated domains (LADs) in which sections of chromosomes are in close opposition with the lamin meshwork ( Mohanta et al, 2021 ; Wong et al, 2021 ). In fact, in some cell types, LADs represent up to half of the genome ( Briand & Collas, 2020 ; Mohanta et al, 2021 ; Rullens & Kind, 2021 ). In general, LADs are relatively gene poor and lack active transcription.…”

Section: Discussionmentioning

confidence: 99%

Effects of mutant lamins on nucleo-cytoskeletal coupling in Drosophila models of LMNA muscular dystrophy

Shaw

Rios-Monterrosa

Fedorchak

et al. 2022

Front. Cell Dev. Biol.

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The nuclei of multinucleated skeletal muscles experience substantial external force during development and muscle contraction. Protection from such forces is partly provided by lamins, intermediate filaments that form a scaffold lining the inner nuclear membrane. Lamins play a myriad of roles, including maintenance of nuclear shape and stability, mediation of nuclear mechanoresponses, and nucleo-cytoskeletal coupling. Herein, we investigate how disease-causing mutant lamins alter myonuclear properties in response to mechanical force. This was accomplished via a novel application of a micropipette harpooning assay applied to larval body wall muscles of Drosophila models of lamin-associated muscular dystrophy. The assay enables the measurement of both nuclear deformability and intracellular force transmission between the cytoskeleton and nuclear interior in intact muscle fibers. Our studies revealed that specific mutant lamins increase nuclear deformability while other mutant lamins cause nucleo-cytoskeletal coupling defects, which were associated with loss of microtubular nuclear caging. We found that microtubule caging of the nucleus depended on Msp300, a KASH domain protein that is a component of the linker of nucleoskeleton and cytoskeleton (LINC) complex. Taken together, these findings identified residues in lamins required for connecting the nucleus to the cytoskeleton and suggest that not all muscle disease-causing mutant lamins produce similar defects in subcellular mechanics.

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“…5,10,12,13 The multidimensional genome organization of eukaryotes can be described in the following order, from large to small: chromosome territories (CTs), chromatin compartments, topologically associating domains (TADs), chromatin loops (Figure 1). 14 These structures are associated with gene expression in multiple dimensions and thereby influence the progression of cell fate transitions.…”

Section: Hierarchical Structure Of the 3d Genomementioning

confidence: 99%

3D genome perspective on cell fate determination, organ regeneration, and diseases

Zhong

Zhang

et al. 2023

Cell Proliferation

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The nucleosome is the fundamental subunit of chromatin. Nucleosome structures are formed by the combination of histone octamers and genomic DNA. Through a systematic and precise process of folding and compression, these structures form a 30‐nm chromatin fibre that is further organized within the nucleus in a hierarchical manner, known as the 3D genome. Understanding the intricacies of chromatin structure and the regulatory mode governing chromatin interactions is essential for unravelling the complexities of cellular architecture and function, particularly in relation to cell fate determination, regeneration, and the development of diseases. Here, we provide a general overview of the hierarchical structure of chromatin as well as of the evolution of chromatin conformation capture techniques. We also discuss the dynamic regulatory changes in higher‐order chromatin structure that occur during stem cell lineage differentiation and somatic cell reprogramming, potential regulatory insights at the chromatin level in organ regeneration, and aberrant chromatin regulation in diseases.

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The 3D Genome: From Structure to Function

Cited by 20 publications

References 296 publications

Three‐dimensional genome structure and function

Three‐dimensional genome structure and function

Effects of mutant lamins on nucleo-cytoskeletal coupling in Drosophila models of LMNA muscular dystrophy

3D genome perspective on cell fate determination, organ regeneration, and diseases

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