Background: Delimiting distinct chromatin domains is essential for temporal and spatial regulation of gene expression. Within the X-inactivation centre region (Xic), the Xist locus, which triggers X-inactivation, is juxtaposed to a large domain of H3K27 trimethylation (H3K27me3).
Results: We describe here that developmentally regulated transcription of Tsix, a crucial non-coding antisense to Xist, is required to block the spreading of the H3K27me3 domain to the adjacent H3K4me2-rich Xist region. Analyses of a series of distinct Tsix mutations suggest that the underlying mechanism involves the RNA Polymerase II accumulating at the Tsix 3'-end. Furthermore, we report additional unexpected long-range effects of Tsix on the distal sub-region of the Xic, involved in Xic-Xic trans-interactions.
Conclusion: These data point toward a role for transcription of non-coding RNAs as a developmental strategy for the establishment of functionally distinct domains within the mammalian genome.
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http://dx.doi.org/10.1186/1756-8935-2-8 | DOI Listing |
Mol Cancer Res
January 2025
The University of Texas Southwestern Medical Center, Dallas, TX, United States.
Elevated blood levels of estrogens are associated with poor prognosis in estrogen receptor-positive (ER+) breast cancers, but the relationship between circulating blood hormone levels and intracellular hormone concentrations are not well characterized. We observed that MCF-7 cells treated acutely with 17β-estradiol (E2) retain a substantial amount of the hormone even upon removal of the hormone from the culture medium. Moreover, global patterns of E2-dependent gene expression are sustained for hours after acute E2 treatment and hormone removal.
View Article and Find Full Text PDFTransplantation
January 2025
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Background: Hepatic ischemia/reperfusion (I/R) injury (HIRI) is an intrinsic phenomenon observed in the process of various liver surgeries. Unfortunately, there are currently few options available to prevent HIRI. Accordingly, we aim to explore the role and key downstream effects of B-cell lymphoma 6 (BCL6) in hepatic I/R (HIR).
View Article and Find Full Text PDFJ Biomed Sci
January 2025
Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
Background: Recent studies indicate that N6-methyladenosine (mA) RNA modification may regulate ferroptosis in cancer cells, while its molecular mechanisms require further investigation.
Methods: Liquid Chromatography-Tandem Mass Spectrometry (HPLC/MS/MS) was used to detect changes in mA levels in cells. Transmission electron microscopy and flow cytometry were used to detect mitochondrial reactive oxygen species (ROS).
Sci Data
January 2025
The Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
The Homo sapiens Chromosomal Location Ontology (HSCLO) is designed to facilitate the integration of human genomic features into biomedical knowledge graphs from releases GRCh37 and GRCh38 at multiple resolutions. HSCLO comprises two distinct versions, HSCLO37 and HSCLO38, each tailored to its respective human genome release. This ontology supports the efficient integration and analysis of human genomic data across scales ranging from entire chromosomes to individual base pairs, thereby enhancing data retrieval and interoperability within large-scale biomedical datasets.
View Article and Find Full Text PDFAm J Hum Genet
January 2025
Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany; Institute of Clinical Human Genetics, University Hospital Regensburg, 93053 Regensburg, Germany. Electronic address:
BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.
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