Determinants of mammalian nucleolar architecture

Farley, Katherine I.; Surovtseva, Yulia V.; Merkel, Janie; Baserga, Susan J.

doi:10.1007/s00412-015-0507-z

Cited by 86 publications

(87 citation statements)

References 73 publications

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“…2). This is the most common condition in reptiles [Olmo and Signorino, 2005], amphibians [King et al, 1990;Schmid and Steinlein, 2015], and fish [Gornung, 2013], although some species in these lineages possess multiple NORs, as do humans, other mammals [Prieto and McStay, 2008;Farley et al, 2015], and birds [de Oliveira Barbosa et al, 2013]. Importantly, existing data indicate that previous reports of multiple NORs in turtles are in error, likely because they were based on the secondary constriction method.…”

Section: Turtle Nor Evolutionmentioning

confidence: 54%

Cytogenetic Insights into the Evolution of Chromosomes and Sex Determination Reveal Striking Homology of Turtle Sex Chromosomes to Amphibian Autosomes

Montiel

Badenhorst²,

Lee³

et al. 2016

Cytogenet Genome Res

136

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Turtle karyotypes are highly conserved compared to other vertebrates; yet, variation in diploid number (2n = 26-68) reflects profound genomic reorganization, which correlates with evolutionary turnovers in sex determination. We evaluate the published literature and newly collected comparative cytogenetic data (G- and C-banding, 18S-NOR, and telomere-FISH mapping) from 13 species spanning 2n = 28-68 to revisit turtle genome evolution and sex determination. Interstitial telomeric sites were detected in multiple lineages that underwent diploid number and sex determination turnovers, suggesting chromosomal rearrangements. C-banding revealed potential interspecific variation in centromere composition and interstitial heterochromatin at secondary constrictions. 18S-NORs were detected in secondary constrictions in a single chromosomal pair per species, refuting previous reports of multiple NORs in turtles. 18S-NORs are linked to ZW chromosomes in Apalone and Pelodiscus and to X (not Y) in Staurotypus. Notably, comparative genomics across amniotes revealed that the sex chromosomes of several turtles, as well as mammals and some lizards, are homologous to components of Xenopus tropicalis XTR1 (carrying Dmrt1). Other turtle sex chromosomes are homologous to XTR4 (carrying Wt1). Interestingly, all known turtle sex chromosomes, except in Trionychidae, evolved via inversions around Dmrt1 or Wt1. Thus, XTR1 appears to represent an amniote proto-sex chromosome (perhaps linked ancestrally to XTR4) that gave rise to turtle and other amniote sex chromosomes.

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Section: Turtle Nor Evolutionmentioning

confidence: 54%

Cytogenetic Insights into the Evolution of Chromosomes and Sex Determination Reveal Striking Homology of Turtle Sex Chromosomes to Amphibian Autosomes

Montiel

Badenhorst²,

Lee³

et al. 2016

Cytogenet Genome Res

136

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“…The first phase involves chromosome movement and the establishment of the PNH, and the second phase involves fusion of nucleolar material associated with individual NORs by a liquidlike behavior. In many human cancer cell lines, nucleoli exhibit an altered morphology-usually larger, more disorganized, and without a clearly visible PNH (Farley et al 2015). This altered morphology appears to be reversible (Krystosek 1998).…”

Section: The Nucleolar Cyclementioning

confidence: 99%

“…Nucleoli of higher eukaryotes are comprised of three distinct subcompartments that can be seen in the electron microscope (Pederson 2010;Farley et al 2015). The innermost fibrillar centers (FCs) are surrounded by dense fibrillar components (DFCs).…”

Section: The Nucleolar Cyclementioning

confidence: 99%

Nucleolar organizer regions: genomic ‘dark matter’ requiring illumination

2016

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Nucleoli form around tandem arrays of a ribosomal gene repeat, termed nucleolar organizer regions (NORs). During metaphase, active NORs adopt a characteristic undercondensed morphology. Recent evidence indicates that the HMG-box-containing DNA-binding protein UBF (upstream binding factor) is directly responsible for this morphology and provides a mitotic bookmark to ensure rapid nucleolar formation beginning in telophase in human cells. This is likely to be a widely employed strategy, as UBF is present throughout metazoans. In higher eukaryotes, NORs are typically located within regions of chromosomes that form perinucleolar heterochromatin during interphase. Typically, the genomic architecture of NORs and the chromosomal regions within which they lie is very poorly described, yet recent evidence points to a role for context in their function. In Arabidopsis, NOR silencing appears to be controlled by sequences outside the rDNA (ribosomal DNA) array. Translocations reveal a role for context in the expression of the NOR on the X chromosome in Drosophila. Recent work has begun on characterizing the genomic architecture of human NORs. A role for distal sequences located in perinucleolar heterochromatin has been inferred, as they exhibit a complex transcriptionally active chromatin structure. Links between rDNA genomic stability and aging in Saccharomyces cerevisiae are now well established, and indications are emerging that this is important in aging and replicative senescence in higher eukaryotes. This, combined with the fact that rDNA arrays are recombinational hot spots in cancer cells, has focused attention on DNA damage responses in NORs. The introduction of DNA double-strand breaks into rDNA arrays leads to a dramatic reorganization of nucleolar structure. Damaged rDNA repeats move from the nucleolar interior to form caps at the nucleolar periphery, presumably to facilitate repair, suggesting that the chromosomal context of human NORs contributes to their genomic stability. The inclusion of NORs and their surrounding chromosomal environments in future genome drafts now becomes a priority.The relationship between nucleolar organizer regions (NORs) and nucleoli was first established in the 1930s (Heitz 1931;McClintock 1934), but, for decades, the content of the former and the role of the latter remained mysterious. The era of molecular and cellular biology revealed that NORs contain tandem arrays of ribosomal gene (rDNA) repeats and that nucleoli are the sites of ribosome biogenesis. Biochemistry has revealed the inner workings of the nucleolus and the complexity of ribosome biogenesis (for review, see Pederson 2010). However, the genomic architecture of NORs and the chromosomal context in which they lie remains undetermined for most eukaryotes. The resulting void has placed limitations on our understanding of the fundamental mechanisms by which NORs orchestrate formation of the largest structure in the nucleus. In this review, I discuss recent findings regarding the morphology of active NORs and how they seed r...

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“…The sequences of DNA encoding these rRNAs colocalize within the nucleus, forming so-called "nucleolar organizing regions" surrounding the nucleolus (37). Mammalian genomes contain Ͼ100 repeats of ribosomal DNA units (38).…”

Section: 6mentioning

confidence: 99%

Reciprocal Regulation of the Cardiac Epigenome by Chromatin Structural Proteins Hmgb and Ctcf

Monte

Rosa‐Garrido

Karbassi

et al. 2016

Journal of Biological Chemistry

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Transcriptome remodeling in heart disease occurs through the coordinated actions of transcription factors, histone modifications, and other chromatin features at pathology-associated genes. The extent to which genome-wide chromatin reorganization also contributes to the resultant changes in gene expression remains unknown. We examined the roles of two chromatin structural proteins, Ctcf (CCCTC-binding factor) and Hmgb2 (high mobility group protein B2), in regulating pathologic transcription and chromatin remodeling. Our data demonstrate a reciprocal relationship between Hmgb2 and Ctcf in controlling aspects of chromatin structure and gene expression. Both proteins regulate each others' expression as well as transcription in cardiac myocytes; however, only Hmgb2 does so in a manner that involves global reprogramming of chromatin accessibility. We demonstrate that the actions of Hmgb2 on local chromatin accessibility are conserved across genomic loci, whereas the effects on transcription are loci-dependent and emerge in concert with histone modification and other chromatin features. Finally, although both proteins share gene targets, Hmgb2 and Ctcf, neither binds these genes simultaneously nor do they physically colocalize in myocyte nuclei. Our study uncovers a previously unknown relationship between these two ubiquitous chromatin proteins and provides a mechanistic explanation for how Hmgb2 regulates gene expression and cellular phenotype. Furthermore, we provide direct evidence for structural remodeling of chromatin on a genome-wide scale in the setting of cardiac disease.

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Determinants of mammalian nucleolar architecture

Cited by 86 publications

References 73 publications

Cytogenetic Insights into the Evolution of Chromosomes and Sex Determination Reveal Striking Homology of Turtle Sex Chromosomes to Amphibian Autosomes

Cytogenetic Insights into the Evolution of Chromosomes and Sex Determination Reveal Striking Homology of Turtle Sex Chromosomes to Amphibian Autosomes

Nucleolar organizer regions: genomic ‘dark matter’ requiring illumination

Reciprocal Regulation of the Cardiac Epigenome by Chromatin Structural Proteins Hmgb and Ctcf

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