Publications by authors named "Jennifer L Gerton"

The ovary is one of the first organs to exhibit signs of aging, characterized by reduced tissue function, chronic inflammation, and fibrosis. Multinucleated giant cells (MNGCs), formed by macrophage fusion, typically occur in chronic immune pathologies, including infectious and non-infectious granulomas and the foreign body response , but are also observed in the aging ovary . The function and consequence of ovarian MNGCs remain unknown as their biological activity is highly context-dependent, and their large size has limited their isolation and analysis through technologies such as single-cell RNA sequencing.

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  • Eukaryotic genomes, like those in humans, often contain large arrays of satellite DNA, such as Human Satellite 3 (HSat3), that are not well understood, especially in terms of their function outside of centromere biology.
  • HSat3 comprises about 2% of the human genome, forms massive arrays, and has been largely excluded from genomic studies until recently, leading to a lack of knowledge about its functional roles.
  • Recent research uncovered that HSat3 has a high density of transcription factor (TF) motifs, particularly related to the Hippo signaling pathway, and reveals that the TEAD transcription factor interacts with the co-activator YAP at HSat3 regions, suggesting a novel link between
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Robertsonian chromosomes are a type of variant chromosome found commonly in nature. Present in one in 800 humans, these chromosomes can underlie infertility, trisomies, and increased cancer incidence. Recognized cytogenetically for more than a century, their origins have remained mysterious.

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Ribosomal RNA (rRNA) genes exist in multiple copies arranged in tandem arrays known as ribosomal DNA (rDNA). The total number of gene copies is variable, and the mechanisms buffering this copy number variation remain unresolved. We surveyed the number, distribution, and activity of rDNA arrays at the level of individual chromosomes across multiple human and primate genomes.

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In this issue of Cell Genomics, Rothschild et al. reveal how ribosomal RNA diversity impacts ribosome structure and its implications for health and disease. Their innovative methodologies uncover distinct ribosome subtypes with significant structural variations and expression patterns.

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  • The study presents detailed genomes of six ape species, achieving high accuracy and complete sequencing of all their chromosomes.
  • It addresses complex genomic regions, leading to enhanced understanding of evolutionary relationships among these species.
  • The findings will serve as a crucial resource for future research on human evolution and our closest ape relatives.
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Karyotypes, composed of chromosomes, must be accurately partitioned by the mitotic spindle for optimal cell health. However, it is unknown how underlying characteristics of karyotypes, such as chromosome number and size, govern the scaling of the mitotic spindle to ensure accurate chromosome segregation and cell proliferation. We utilize budding yeast strains engineered with fewer chromosomes, including just two "mega chromosomes," to study how spindle size and function are responsive to, and scaled by, karyotype.

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Nucleolar morphology is a well-established indicator of ribosome biogenesis activity that has served as the foundation of many screens investigating ribosome production. Missing from this field of study is a broad-scale investigation of the regulation of ribosomal DNA morphology, despite the essential role of rRNA gene transcription in modulating ribosome output. We hypothesized that the morphology of rDNA arrays reflects ribosome biogenesis activity.

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  • Apes have two sex chromosomes: the essential Y chromosome for male reproduction and the X chromosome necessary for both reproduction and cognition, with differences in mating patterns affecting their function.
  • Studying these chromosomes is challenging due to their repetitive structures, but researchers created gapless assemblies for five great apes and one lesser ape to explore their evolutionary complexities.
  • The Y chromosomes are highly variable and undergo significant changes compared to the more stable X chromosomes, and this research can provide insights into human evolution and aid in the conservation of endangered ape species.
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Robertsonian chromosomes form by fusion of two chromosomes that have centromeres located near their ends, known as acrocentric or telocentric chromosomes. This fusion creates a new metacentric chromosome and is a major mechanism of karyotype evolution and speciation. Robertsonian chromosomes are common in nature and were first described in grasshoppers by the zoologist W.

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  • Human centromeres are challenging to sequence due to their large size and repetitive nature, limiting our understanding of their variation and evolutionary function.
  • Using long-read sequencing, researchers completely sequenced and assembled all centromeres from a second human genome, revealing a significant increase in genetic variation and size differences between centromeres.
  • Comparative analysis of centromeric sequences across species, including humans and great apes, highlights the rapid evolution of α-satellite DNA and suggests limited recombination between chromosome arms, aiding in studying centromeric DNA evolution.
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Ribosome biogenesis is a vital and highly energy-consuming cellular function occurring primarily in the nucleolus. Cancer cells have an elevated demand for ribosomes to sustain continuous proliferation. This study evaluated the impact of existing anticancer drugs on the nucleolus by screening a library of anticancer compounds for drugs that induce nucleolar stress.

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  • Apes have two main sex chromosomes, X and Y, where Y is crucial for male reproduction and its deletions can lead to infertility, while X is important for both reproduction and brain function.
  • Recent advancements in genomic techniques helped researchers create complete structures of the X and Y chromosomes for multiple great ape species, allowing them to explore their evolutionary complexities.
  • Findings indicate that Y chromosomes are highly variable and undergo rapid changes due to unique genetic regions and transposable elements, while X chromosomes are more stable, highlighting differing evolutionary paths among great ape species.
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The centromere components cohesin, CENP-A, and centromeric DNA are essential for biorientation of sister chromatids on the mitotic spindle and accurate sister chromatid segregation. Insight into the 3D organization of centromere components would help resolve how centromeres function on the mitotic spindle. We use ChIP-seq and super-resolution microscopy with single particle averaging to examine the geometry of essential centromeric components on human chromosomes.

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The human Y chromosome has been notoriously difficult to sequence and assemble because of its complex repeat structure that includes long palindromes, tandem repeats and segmental duplications. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference, showing the complete ampliconic structures of gene families TSPY, DAZ and RBMY; 41 additional protein-coding genes, mostly from the TSPY family; and an alternating pattern of human satellite 1 and 3 blocks in the heterochromatic Yq12 region.

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We completely sequenced and assembled all centromeres from a second human genome and used two reference sets to benchmark genetic, epigenetic, and evolutionary variation within centromeres from a diversity panel of humans and apes. We find that centromere single-nucleotide variation can increase by up to 4.1-fold relative to other genomic regions, with the caveat that up to 45.

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The placenta is essential for reproductive success. The murine placenta includes polyploid giant cells that are crucial for its function. Polyploidy occurs broadly in nature but its regulators and significance in the placenta are unknown.

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The biorientation of sister chromatids on the mitotic spindle, essential for accurate sister chromatid segregation, relies on critical centromere components including cohesin, the centromere-specific H3 variant CENP-A, and centromeric DNA. Centromeric DNA is highly variable between chromosomes yet must accomplish a similar function. Moreover, how the 50 nm cohesin ring, proposed to encircle sister chromatids, accommodates inter-sister centromeric distances of hundreds of nanometers on the metaphase spindle is a conundrum.

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Article Synopsis
  • The research investigates the short arms of human acrocentric chromosomes (13, 14, 15, 21, and 22), revealing large homologous regions that suggest ongoing recombination rather than simply being ancestral traits.
  • Using comprehensive data from the Human Pangenome Reference Consortium, the study identifies pseudo-homologous regions (PHRs) within these chromosomes, indicating frequent genetic exchanges between non-homologous sequences, which could lead to variations in genetic traits.
  • The findings support the idea that these regions are linked to Robertsonian translocations, indicating that modern genetic studies reaffirm old cytogenetic theories about chromosome interactions dating back 50 years.
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Eukaryotic genomes maintain multiple copies of ribosomal DNA gene repeats in tandem arrays to provide sufficient ribosomal RNAs to make ribosomes. These DNA repeats are the most highly transcribed regions of the genome, with dedicated transcriptional machinery to manage the enormous task of producing more than 50% of the total RNA in a proliferating cell. The arrays are called nucleolar organizer regions (NORs) and constitute the scaffold of the nucleolar compartment, where ribosome biogenesis occurs.

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The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has benefitted society. However, it still has many gaps and errors, and does not represent a biological genome as it is a blend of multiple individuals. Recently, a high-quality telomere-to-telomere reference, CHM13, was generated with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a nearly homozygous genome.

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The ring-like cohesin complex plays an essential role in chromosome segregation, organization, and double-strand break repair through its ability to bring two DNA double helices together. Scc2 (NIPBL in humans) together with Scc4 functions as the loader of cohesin onto chromosomes. Chromatin adapters such as the RSC complex facilitate the localization of the Scc2-Scc4 cohesin loader.

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Mobile elements and repetitive genomic regions are sources of lineage-specific genomic innovation and uniquely fingerprint individual genomes. Comprehensive analyses of such repeat elements, including those found in more complex regions of the genome, require a complete, linear genome assembly. We present a de novo repeat discovery and annotation of the T2T-CHM13 human reference genome.

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Since its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome, leaving important heterochromatic regions unfinished. Addressing the remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium presents a complete 3.055 billion-base pair sequence of a human genome, T2T-CHM13, that includes gapless assemblies for all chromosomes except Y, corrects errors in the prior references, and introduces nearly 200 million base pairs of sequence containing 1956 gene predictions, 99 of which are predicted to be protein coding.

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Existing human genome assemblies have almost entirely excluded repetitive sequences within and near centromeres, limiting our understanding of their organization, evolution, and functions, which include facilitating proper chromosome segregation. Now, a complete, telomere-to-telomere human genome assembly (T2T-CHM13) has enabled us to comprehensively characterize pericentromeric and centromeric repeats, which constitute 6.2% of the genome (189.

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