Differences in centromere positioning of cycling and postmitotic human cell types

Solovei, Irina; Schermelleh, Lothar; Düring, Klaus; Engelhardt, A.; Stein, Stefan; Cremer, Christoph; Cremer, Thomas

doi:10.1007/s00412-004-0287-3

Cited by 87 publications

(93 citation statements)

References 45 publications

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“…Moreover, due to the linear proximity of centromeres to NORs, PCH often colocalizes with PNH. [28][29][30][31][32] Our ImmunoFISH analysis of late replicating loci on small chromosomes (chr19, 20, 21 and 22) simultaneously with the 3 repressive subcompartments of PH, PCH and PNH clearly shows that even on chromosomes 19 and 22, which exhibit very little peripheral localization, the late loci largely remain associated with a repressive subcompartment (Fig. 3, Supplemental Tables 2, 3).…”

Section: Discussionmentioning

confidence: 88%

Functional redundancy in the nuclear compartmentalization of the late-replicating genome

Ragoczy

Telling

Scalzo

et al. 2014

Nucleus

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The eukaryotic nucleus is structurally and functionally organized, as reflected in the distribution of its protein and DNA components. The genome itself is segregated into euchromatin and heterochromatin that replicate in a distinct spatio-temporal manner. We used a combination of fluorescence in situ hybridization (FISH) and DamID to investigate the localization of the early and late replicating components of the genome in a lymphoblastoid cell background. Our analyses revealed that the bulk of late replicating chromatin localizes to the nuclear peripheral heterochromatin (PH) in a chromosome size and gene density dependent manner. Late replicating DNA on small chromosomes exhibits a much lower tendency to localize to PH and tends to associate with alternate repressive subcompartments such as pericentromeric (PCH) and perinucleolar heterochromatin (PNH). Furthermore, multicolor FISH analysis revealed that late replicating loci, particularly on the smaller chromosomes, may associate with any of these 3 repressive subcompartments, including more than one at the same time. These results suggest a functional equivalence or redundancy among the 3 subcompartments. Consistent with this notion, disruption of nucleoli resulted in an increased association of late replicating loci with peripheral heterochromatin. Our analysis reveals that rather than considering the morphologically distinct PH, PCH and PNH as individual subcompartments, they should be considered in aggregate as a functional compartment for late replicating chromatin.

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Section: Discussionmentioning

confidence: 88%

Functional redundancy in the nuclear compartmentalization of the late-replicating genome

Ragoczy

Telling

Scalzo

et al. 2014

Nucleus

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“…Centromere position was well studied using 3D image analysis in a number of human cell types (lymphocytes, fibroblasts, lymphoblastoid, and neuroblastoma cells) as well as the different stages of cell cycling [Solovei et al 2004]. Solovei and colleagues reported similar changes of centromere position during cell cycles with the formation of centromeric clusters during late G1 and early S phase of mitosis in all types of analyzed cells.…”

Section: Discussionmentioning

confidence: 99%

The three-dimensional image analysis of the chromocenter in motile and immotile human sperm

Alladin¹,

Moskovtsev²,

Russell³

et al. 2013

Systems Biology in Reproductive Medicine

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Chromosomes in human spermatozoa are arranged nonrandomly with the centromeres of non-homologous chromosomes forming a chromocenter. We have compared motile and immotile sperm populations in normozoospermic patients to determine if there is any dissimilarity in the formation of the chromocenter and the nuclear position of chromosome 17. Based on the differences between motile and immotile populations, we propose for the 'optimal' nuclear organization to be defined as containing 1 to 3 chromocenter(s) with central radial and median longitudinal position for the centromere of chromosome 17. By this definition, 42% of motile spermatozoa had 'optima' nuclei, in comparison to 25% of immotile spermatozoa (P < 0.05). Immotile spermatozoa exhibited a greater disruption in the formation of the chromocenter, altered position of the centromere of chromosome 17, and were more prone to chemical decondensation, resulting in higher nuclear and chromocenter volumes. The altered topology of the chromosomes might lead to the disruption of the sequence of events involved in fertilization and early embryonic development.

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“…Individual chromosomes are typically oriented with their centromeres situated in the nuclear periphery (29), while telomeres are distributed throughout the nucleoplasm (30). In the multilobulated E145K, nuclei chromosomes are organized with their centromeres clustered in one region.…”

Section: Discussionmentioning

confidence: 99%

A progeria mutation reveals functions for lamin A in nuclear assembly, architecture, and chromosome organization

Taimen

Pfleghaar²,

Shimi

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

195

215

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Numerous mutations in the humancomprising the major structural components of the nuclear lamina, the fibrous meshwork underlying the inner nuclear membrane (1). They are major determinants of nuclear size and shape and are involved in essential functions such as DNA replication and transcription (1). Lamins A (LA) and C (LC) are alternatively spliced products of the LMNA gene, whereas lamins LB1 and LB2 are encoded by LMNB1 and LMNB2. Structurally, the lamins have a conserved central ␣-helical rod domain flanked by globular head and tail domains. The central rod is responsible for the formation of in-parallel and in-register coiled-coil dimers, the building blocks of lamin polymers. In vitro, lamin dimers form head-to-tail chains, which further interact laterally in an anti-parallel orientation to form highly ordered paracrystals (PCs) (2). However, little is known about the assembly of lamins into higher order structures in vivo.There are Ͼ250 mutations in human LMNA causing a wide range of diseases [for detail, see http//www.umd.be/LMNA/ and (3)]. Among these is the rare premature aging disease, Hutchinson-Gilford progeria syndrome (HGPS). HGPS children typically appear normal at birth, but show growth retardation before the age of 2 years. Further manifestations include loss of hair, lipodystrophy, sclerodermatous skin, osteolysis, and progressive atherosclerosis leading to death at an average age of 13 years due to myocardial infarcts and strokes (4). Most HGPS patients carry the 1824CϾT mutation (G608G), which activates a cryptic splice site resulting in the expression of LA with 50 amino acids deleted near its C terminus (LA⌬50/progerin) (5). As a result, LA⌬50/ progerin remains permanently farnesylated (6, 7), and its accumulation in patients' cells is correlated with the loss of heterochromatin and changes in histone methylation (1).In addition to 1824CϾT, there are 21 other LMNA mutations causing progeria (http://www.umd.be/LMNA/). Some of these are located in the central rod domain, where they could directly impact the assembly of lamins into dimers and higher order structures. Here, we have studied the alterations in nuclear architecture and chromatin organization in one of these mutations, 433GϾA (E145K), located in segment 1B of the central rod domain of LA/C (5). A patient bearing this mutation showed earlier onset cardiovascular defects, only partial loss of hair and ample s.c. fat (5). We show that fibroblasts derived from an E145K patient have severely misshapen nuclei and multiple defects in chromatin organization as reflected by centromere clustering and an abnormal distribution of telomeres throughout the cell cycle. These abnormalities are established during cell division as nuclei assemble in daughter cells. The results demonstrate that the nuclear changes in E145K progeria cells are significantly different from those seen in cells expressing LA⌬50/ progerin, and they also emphasize the essential role of lamins in establishing and maintaining nuclear architecture.

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Differences in centromere positioning of cycling and postmitotic human cell types

Cited by 87 publications

References 45 publications

Functional redundancy in the nuclear compartmentalization of the late-replicating genome

Functional redundancy in the nuclear compartmentalization of the late-replicating genome

The three-dimensional image analysis of the chromocenter in motile and immotile human sperm

A progeria mutation reveals functions for lamin A in nuclear assembly, architecture, and chromosome organization

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