Distinct nuclear compartment-associated genome architecture in the developing mammalian brain

Ahanger, Sajad Hamid; Delgado, Ryan N.; Gil, Eugene; Cole, Mitchel A; Jin, Zhao; Hong, Sung Jun; Kriegstein, Arnold R; Nowakowski, Tomasz J.; Pollen, Alex A.; Lim, Daniel A.

doi:10.1038/s41593-021-00879-5

Cited by 47 publications

(52 citation statements)

References 49 publications

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“…Besides the repressive regulation of the LAD-associated genes, the NL itself could also regulate developmental genes in a range of tissues, and its disruption often leads to diseases. For instance, a critical role of LAD architecture in mouse and human brain development as well as brain diseases has been reviewed by Ahanger et al [ 56 ].…”

Section: Types Of 3d Chromatin Architecturementioning

confidence: 99%

3D chromatin architecture and transcription regulation in cancer

2022

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Chromatin has distinct three-dimensional (3D) architectures important in key biological processes, such as cell cycle, replication, differentiation, and transcription regulation. In turn, aberrant 3D structures play a vital role in developing abnormalities and diseases such as cancer. This review discusses key 3D chromatin structures (topologically associating domain, lamina-associated domain, and enhancer–promoter interactions) and corresponding structural protein elements mediating 3D chromatin interactions [CCCTC-binding factor, polycomb group protein, cohesin, and Brother of the Regulator of Imprinted Sites (BORIS) protein] with a highlight of their associations with cancer. We also summarise the recent development of technologies and bioinformatics approaches to study the 3D chromatin interactions in gene expression regulation, including crosslinking and proximity ligation methods in the bulk cell population (ChIA-PET and HiChIP) or single-molecule resolution (ChIA-drop), and methods other than proximity ligation, such as GAM, SPRITE, and super-resolution microscopy techniques.

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Section: Types Of 3d Chromatin Architecturementioning

confidence: 99%

3D chromatin architecture and transcription regulation in cancer

2022

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“…The depletion of lamin B1 leads to the detachment of LADs from the periphery, global chromatin redistribution towards the nuclear center and chromatin de-compaction in cultured cells [ 56 ]. A recent study additionally found that in the embryonic forebrain, dorsal relative to ventral neural progenitors have different LAD architectures that in turn reflect their gene expression patterns [ 57 ].…”

Section: Nuclear Envelope In Chromatin Regulationmentioning

confidence: 99%

“…Enzymatic extraction of LADs from mouse embryonic NSCs followed by H3k9me2 chromatin immunoprecipitation sequencing (ChIP-seq) revealed that the actively transcribed genes were not bound to H3k9me2. These results suggest that gene silencing within LADs can only occur in combination with this epigenetic modification [ 57 ]. Thus, gene association with various elements of the NE and histone modifications represent two complementary layers of gene regulation that operate during cell differentiation.…”

Section: Nuclear Envelope In Chromatin Regulationmentioning

confidence: 99%

A Nuclear Belt Fastens on Neural Cell Fate

Mestres

Houtman

Calegari

et al. 2022

Cells

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Successful embryonic and adult neurogenesis require proliferating neural stem and progenitor cells that are intrinsically and extrinsically guided into a neuronal fate. In turn, migration of new-born neurons underlies the complex cytoarchitecture of the brain. Proliferation and migration are therefore essential for brain development, homeostasis and function in adulthood. Among several tightly regulated processes involved in brain formation and function, recent evidence points to the nuclear envelope (NE) and NE-associated components as critical new contributors. Classically, the NE was thought to merely represent a barrier mediating selective exchange between the cytoplasm and nucleoplasm. However, research over the past two decades has highlighted more sophisticated and diverse roles for NE components in progenitor fate choice and migration of their progeny by tuning gene expression via interactions with chromatin, transcription factors and epigenetic factors. Defects in NE components lead to neurodevelopmental impairments, whereas age-related changes in NE components are proposed to influence neurodegenerative diseases. Thus, understanding the roles of NE components in brain development, maintenance and aging is likely to reveal new pathophysiological mechanisms for intervention. Here, we review recent findings for the previously underrepresented contribution of the NE in neuronal commitment and migration, and envision future avenues for investigation.

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“…The complex machinery for intranuclear topography maintenance also includes nuclear transmembrane proteins that are responsible for gene repositioning, during myogenesis, in order to shift the genes to be repressed to more peripheral positions (Robson et al 2016;Ahanger et al 2021). Those peripheral domains are mainly low gene expression regions that contain histone marks of a silenced state (Smith et al 2021).…”

Section: Influence Of Genomic Arrangement In the Nucleus On Aneuploidymentioning

confidence: 99%

A Multilevel Approach to the Causes of Genetic Instability in Stem Cells

González

2022

Handbook of Stem Cell Therapy

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This chapter addresses the genetic instability in stem cells, a central feature that is an important determinant for the safety and effectiveness of cell-based therapies. First, DNA damage response mechanism and the gene network that regulates the DNA integrity homeostasis are revisited, focusing on relationship between genetic integrity and stemness maintenance. Also, several factors have been included that influence genetic instability in vivo, i.e., ROS generation and inflammation, and in vitro regarding cell isolation, culture conditions, i.e., oxygen levels and the use of feeder layers and different carriers, splitting procedures, passage number, etc. Telomere shortening, replicative senescence aneuploidy, and the senescence-associated secretory phenotype are different processes involved in deterioration of stem cells abilities for homing, reparability, and paracrine modulation. Moreover, less effective DNA repair upon senescence increases the propensity of developing tumors for stem cells that is one the main concerns related to genetic instability in stem cells. Nuclear organization and their determinants linked to chromosome aberrations and aneuploidy in stem cells and those epigenetic changes affecting stability are addressed. Differences between adipose, embryonic, and induced pluripotent stem cells are analyzed regarding to their ontogeny, changes in culture, and variation in proliferative capacity and stemness. The effect of reprogramming methods in genetic instability and variation in mutagenicity according to genes utilized for pluripotency induction, i.e., Yamanaka's factors and others, is discussed. Donor-related factors, i.e., age, smoking, and alcohol consumption, comorbidities, i.e., obesity, insulin resistance, diabetes, are mentioned for wide evaluation of genetic instability. The next years must witness consensus protocols that will contribute to control the effects of factors that alter stem cell genetic stability to increase the security and applicability of cell-based therapy.

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Distinct nuclear compartment-associated genome architecture in the developing mammalian brain

Cited by 47 publications

References 49 publications

3D chromatin architecture and transcription regulation in cancer

3D chromatin architecture and transcription regulation in cancer

A Nuclear Belt Fastens on Neural Cell Fate

A Multilevel Approach to the Causes of Genetic Instability in Stem Cells

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