Nucleoli form interchromosomal contacts with genes controlling differentiation and carcinogenesis. DUX4 genes specify transcription factor possessing two homeodomains. Previously, using Circular Chromosome Conformation Capture (4С) approach on population of cells, it was demonstrated that DUX4 gene clusters form frequent contacts with nucleoli. It was found also that these contacts are almost completely abolished after heat shock treatment. 4C approach as all ligation-mediated methods is capable to detect rather close interactions between chromatin loops in nuclei. In order to independently confirm the formation and the frequency of the contacts in single cells we used FISH approach. Here, we show that DUX genes in single cells form stable contacts in all tested HEK293T cells. During heat shock, DUX4 genes reversibly move 1-3 µm away from the nuclei. We conclude that interchromosomal contacts formed by nucleoli are strong, dynamic, and reversible, providing both the initiation and maintenance of a differentiated state.
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http://dx.doi.org/10.1134/S1607672924700935 | DOI Listing |
Skelet Muscle
December 2024
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, MO, USA.
Germline mutations in SMCHD1, DNMT3B and LRIF1 can cause facioscapulohumeral muscular dystrophy type 2 (FSHD2). FSHD is an epigenetic skeletal muscle disorder in which partial failure in heterochromatinization of the D4Z4 macrosatellite repeat causes spurious expression of the repeat-embedded gene in skeletal muscle, ultimately leading to muscle weakness and wasting. All three proteins play a role in chromatin organization and gene silencing; however, their functional relationship has not been fully elucidated.
View Article and Find Full Text PDFBrain
November 2024
Department of Human Genetics, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
Facioscapulohumeral muscular dystrophy (FSHD) is caused by sporadic misexpression of the transcription factor double homeobox 4 (DUX4) in skeletal muscles. So far, monolayer cultures and animal models have been used to study the FSHD disease mechanism and for FSHD therapy development, but these models do not fully recapitulate the disease and there is a lack of knowledge on how DUX4 misexpression leads to skeletal muscle dysfunction. To overcome these barriers, we have developed a three-dimensional tissue engineered skeletal muscle (3D-TESM) model by generating genetically matched myogenic progenitors (MPs) from human induced pluripotent stem cells of three mosaic FSHD patients.
View Article and Find Full Text PDFTransl Cancer Res
October 2024
Department of Oncology, Suzhou Ninth People's Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China.
Background: Capicua transcriptional repressor (CIC)-rearranged sarcoma (CRS) is a rare and highly aggressive undifferentiated small round cell sarcoma (USRCS), which genetically displays a characteristic gene fusion between gene with other genes such as .
Case Description: We report a rare case with fusion. The 45-year-old male patient presented to our department with frequent dry cough and lumbar pain.
Int J Mol Sci
October 2024
NIHR Biomedical Research Centre, University College London, Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Trust, London WC1N 1EH, UK.
DUX4 is the major gene responsible for facioscapulohumeral dystrophy (FSHD). Several mouse models expressing DUX4 have been developed, the most commonly used by academic laboratories being ACTA1-MCM/FLExDUX4. In this study, molecular and histological modifications in the tibialis anterior and quadriceps muscles were investigated in this model at different time points.
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