Chromosomal rearrangements during human epidermal keratinocyte differentiation

Marella, Narasimharao V.; Seifert, Brandon; Nagarajan, Priyadharsini; Sinha, Satrajit; Berezney, Ronald

doi:10.1002/jcp.21855

Cited by 22 publications

(20 citation statements)

References 81 publications

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“…Clustering of short telomeres has been involved in the formation of micronuclei, nucleoplasmic bridges, and nuclear buds [91]. Some evidence suggests that telomere positioning is one of the determinant factors governing chromosome territory [29,91,92,93] whose disruption can affect gene expression [94], generate chromosomal abnormalities [29] and disrupt cell function [95]. Moreover, telomeres occupy microterritories throughout the cell cycle, forming groups of telomeres that have peripheral location.…”

Section: Telomeric Nuclear Organizationmentioning

confidence: 99%

Dynamic Length Changes of Telomeres and Their Nuclear Organization in Chronic Myeloid Leukemia

Samassékou

2013

Cancers

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Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the t(9;22) translocation. As in most cancers, short telomeres are one of the features of CML cells, and telomere shortening accentuates as the disease progresses from the chronic phase to the blastic phase. Although most individual telomeres are short, some of them are lengthened, and long individual telomeres occur non-randomly and might be associated with clonal selection. Telomerase is the main mechanism used to maintain telomere lengths, and its activity increases when CML evolves toward advanced stages. ALT might be another mechanism employed by CML cells to sustain the homeostasis of their telomere lengths and this mechanism seems predominant at the early stage of leukemogenesis. Also, telomerase and ALT might jointly act to maintain telomere lengths at the chronic phase, and as CML progresses, telomerase becomes the major mechanism. Finally, CML cells display an altered nuclear organization of their telomeres which is characterized by the presence of high number of telomeric aggregates, a feature of genomic instability, and differential positioning of telomeres. CML represents a good model to study mechanisms responsible for dynamic changes of individual telomere lengths and the remodeling of telomeric nuclear organization throughout cancer progression.

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Section: Telomeric Nuclear Organizationmentioning

confidence: 99%

Dynamic Length Changes of Telomeres and Their Nuclear Organization in Chronic Myeloid Leukemia

Samassékou

2013

Cancers

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“…In spherical nuclei, CTs have preferred radial positions, in that gene-rich chromosomes tend to be internally located and gene-poor chromosomes are closer to the nuclear periphery [58]. Aside from this general feature, loci organization within a CT [59] and the organization of CTs relative to each other are cell type-specific [60], suggestive of functional relevance. A recent cutting-edge work has brought new insights on the biophysical principles of CT folding.…”

Section: Chromosome Territoriesmentioning

confidence: 99%

3D shortcuts to gene regulation

Hakim

Sung

Hager

2010

Current Opinion in Cell Biology

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Summary of recent advancesRecent technologies have allowed high resolution genome-wide binding profiles of numerous transcription factor and other proteins. A widespread observation has emerged from studies in diverse mammalian systems: most binding events are located at great distances from gene promoters. It is becoming apparent that the traditional one-dimensional view of gene regulation via the proximal cis regulatory elements is over-simplified. True proximity and functional relevance can be revealed by studying the three-dimensional structure of the genome packaged inside the nucleus. Thus the spatial architecture of the genome has attracted a lot of interest and has intensified its significance in modern cell biology. Here we discuss current methods, concepts, and controversies in this rapidly evolving field.

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“…Furthermore, 3D-genome organization also changes during keratinocyte differentiation in vitro , including the position of selected chromosomes and EDC locus relatively to the corresponding chromosome territory (Marella et al , 2009; Williams et al , 2002). …”

Section: Introductionmentioning

confidence: 99%

Remodeling of Three-Dimensional Organization of the Nucleus during Terminal Keratinocyte Differentiation in the Epidermis

Gdula

Poterlowicz

Mardaryev

et al. 2013

Journal of Investigative Dermatology

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The nucleus of epidermal keratinocytes is a complex and highly compartmentalized organelle, whose structure is markedly changed during terminal differentiation and transition of the genome from a transcriptionally active state seen in the basal and spinous epidermal cells to a fully inactive state in the keratinized cells of the cornified layer. Here, using multi-color confocal microscopy, followed by computational image analysis and mathematical modelling, we demonstrate that in normal mouse foot-pad epidermis transition of keratinocytes from basal epidermal layer to the granular layer is accompanied by marked differences in nuclear architecture and micro-environment including: i) decrease of the nuclear volume, ii) decrease in expression of the markers of transcriptionally-active chromatin; iii) internalization and decrease in the number of nucleoli; iv) increase in the number of pericentromeric heterochromatic clusters; v) increase in the frequency of associations between pericentromeric clusters, chromosomal territory 3, and nucleoli. These data suggest a role for nucleoli and pericentromeric heterochromatin clusters as organizers of nuclear micro-environment required for proper execution of gene expression programs in differentiating keratinocytes and provide important background information for further analyses of alterations in the topological genome organization seen in pathological skin conditions including disorders of epidermal differentiation and epidermal tumors.

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Chromosomal rearrangements during human epidermal keratinocyte differentiation

Cited by 22 publications

References 81 publications

Dynamic Length Changes of Telomeres and Their Nuclear Organization in Chronic Myeloid Leukemia

Dynamic Length Changes of Telomeres and Their Nuclear Organization in Chronic Myeloid Leukemia

3D shortcuts to gene regulation

Remodeling of Three-Dimensional Organization of the Nucleus during Terminal Keratinocyte Differentiation in the Epidermis

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