Chromosomes are selectively organized within the nuclei of interphase cells reflecting the current fate of each cell and are reorganized in response to various physiological cues to maintain homeostasis. Although substantial progress is being made to establish the various patterns of genome architecture, less is understood on how chromosome folding/positioning is achieved. Here, we discuss recent insights into the cellular mechanisms dictating chromatin movements including the use of epigenetic modifications and allosterically regulated transcription factors, as well as a nucleoskeleton system comprised of actin, myosin, and actin-binding proteins. Together, these nuclear factors help coordinate the positioning of both general and cell-specific genomic architectural features.
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http://dx.doi.org/10.1016/j.ceb.2020.10.005 | DOI Listing |
Acta Neuropathol
January 2025
Department of Neurology, NYU Grossman School of Medicine, New York, NY, USA.
Down syndrome (DS) is strongly associated with Alzheimer's disease (AD) due to APP overexpression, exhibiting Amyloid-β (Aβ) and Tau pathology similar to early-onset (EOAD) and late-onset AD (LOAD). We evaluated the Aβ plaque proteome of DS, EOAD, and LOAD using unbiased localized proteomics on post-mortem paraffin-embedded tissues from four cohorts (n = 20/group): DS (59.8 ± 4.
View Article and Find Full Text PDFHum Mol Genet
January 2025
Department of Human Genetics, McGill University, 3666 McTavish Street, Montreal, QC H3A 1Y2, Canada.
Many genes in the human genome encode proteins that are dosage sensitive, meaning they require protein levels within a narrow range to properly execute function. To investigate if clinically relevant variation in protein levels impacts the same downstream pathways in human disease, we generated cell models of two SETBP1 syndromes: Schinzel-Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disease (SHD), where SGS is caused by too much protein, and SHD is caused by not enough SETBP1. Using patient and sex-matched healthy first-degree relatives from both SGS and SHD SETBP1 cases, we assessed how SETBP1 protein dosage affects downstream pathways in human forebrain progenitor cells.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Pediatrics, Division of Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Neonatal health is dependent on early risk stratification, diagnosis, and timely management of potentially devastating conditions, particularly in the setting of prematurity. Many of these conditions are poorly predicted in real-time by clinical data and current diagnostics. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Gynecologic Oncology, National Hospital Organization (NHO) Shikoku Cancer Center, Ko-160 Minami-Umemoto, Matsuyama, 7910280, Japan.
Cancer cells in the right subdiaphragmatic lavage may reflect peritoneal dissemination, but its prognostic significance is unknown. This study investigated recurrence-free survival (RFS), overall survival (OS), and recurrence patterns in patients with curatively resected endometrial cancer by cytology collection site. Peritoneal cytology was collected at the beginning of surgery by washing the pelvic and right subdiaphragmatic cavity separately.
View Article and Find Full Text PDFJ Hum Genet
January 2025
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan.
Large-scale population cohort studies that collect genomic information are tasked with returning an assessment of genetic risk for hereditary cancers to participants. While several studies have applied to return identified genetic risks to participants, comprehensive surveys of participants' understanding, feelings, and behaviors toward cancer risk remain to be conducted. Here, we report our experience and surveys of returning genetic risks to 100 carriers of pathogenic variants for hereditary cancers identified through whole genome sequencing of 50 000 individuals from the Tohoku Medical Megabank project, a population cohort study.
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