Multiple layers of regulation are required to ensure appropriate patterns of gene expression for accurate cell differentiation. Interphase chromatin is non-randomly distributed within the nucleus, with highly compacted, transcriptionally silent heterochromatin enriched at the nuclear and nucleolar periphery. Whether this spatial organization serves a function in organismal physiology, rather than simply being a byproduct of chromatin metabolism, is a fundamental question. Recent work performed in C. elegans embryos characterized the molecular mechanisms that drive the perinuclear anchoring of heterochromatin. Moreover, for the first time it was shown that heterochromatin sequestration helps to restrict cell differentiation programs, while sustaining commitment to a specified fate. Here, we describe and comment on these findings, placing them in a broader context.
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http://dx.doi.org/10.1080/19491034.2016.1187354 | DOI Listing |
Pharmacol Res
January 2025
Department of Physiology, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, 430030, PR China. Electronic address:
Pediatric high-grade gliomas (pHGGs) are the most common brain malignancies in children and are characterized by blocked differentiation. The epigenetic landscape of pHGGs, particularly the H3K27-altered and H3G34-mutant subtypes, suggests these tumors may be particularly susceptible to strategies that target blocked differentiation. Differentiation therapy aims to overcome this differentiation blockade by promoting glioma cell differentiation into more mature and less malignant cells.
View Article and Find Full Text PDFCell Stem Cell
January 2025
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn-Children's Hospital of Philadelphia Lung Biology Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:
Functional regeneration of the lung's gas exchange surface following injury requires the coordination of a complex series of cell behaviors within the alveolar niche. Using single-cell transcriptomics combined with lineage tracing of proliferating progenitors, we examined mouse lung regeneration after influenza injury, demonstrating an asynchronously phased response across different cellular compartments. This longitudinal atlas of injury responses has produced a catalog of transient and persistent transcriptional alterations in cells as they transit across axes of differentiation.
View Article and Find Full Text PDFPathol Res Pract
January 2025
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35249, United States. Electronic address:
Estrogen receptor (ER) is a direct and reciprocal target gene for GATA3. Previous studies have shown that higher GATA3 expression in primary breast cancer (BC) is associated with a reduced probability of developing lung metastasis when compared to those with metastatic recurrence to other organs. Further, GATA3 downregulates several genes promoting BC lung metastasis and upregulates genes encoding known inhibitors of lung metastasis.
View Article and Find Full Text PDFCell Rep
January 2025
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:
Chromatin regulatory proteins are expressed broadly and assumed to exert the same intrinsic function across cell types. Here, we report that 14 chromatin regulators undergo evolutionary-conserved neuron-specific splicing events involving microexons. Among them are two components of a histone demethylase complex: LSD1 H3K4 demethylase and the H3K4me0-reader PHF21A.
View Article and Find Full Text PDFJ Physiol
January 2025
Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
Here we characterize seven Cx30.3 gene variants (R22H, S26Y, P61R, C86S, E99K, T130M and M190L) clinically associated with the rare skin disorder erythrokeratodermia variabilis et progressiva (EKVP) in tissue-relevant and differentiation-competent rat epidermal keratinocytes (REKs). We found that all variants, when expressed alone or together with wildtype (WT) Cx30.
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