More and more studies have shown chromatin remodelers and histone modifiers play essential roles in regulating developmental patterns by organizing specific chromosomal architecture to establish programmed transcriptional profiles, with implications that histone chaperones execute a coordinating role in these processes. Chromatin assembly factor-1 (CAF-1), an evolutionarily conserved three-subunit protein complex, was identified as a histone chaperone coupled with DNA replication and repair in cultured mammalian cells and yeasts. Interestingly, recent findings indicate CAF-1 may have important regulatory roles during development by interacting with specific transcription factors and epigenetic regulators. In this review, we focus on the essential roles of CAF-1 in regulating heterochromatin organization, asymmetric cell division, and specific signal transduction through epigenetic modulations of the chromatin. In the end, we aim at providing a current image of facets of CAF-1 as a histone chaperone to orchestrate cell proliferation and differentiation during multi-cellular organism development.
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http://dx.doi.org/10.1007/s00018-014-1748-3 | DOI Listing |
Front Med
January 2025
Guizhou University Medical College, Guiyang, 550025, China.
The p60 subunit of the chromatin assembly factor-1 complex, that is, chromatin assembly factor-1 subunit B (CHAF1B), is a histone H3/H4 chaperone crucial for the transcriptional regulation of cell differentiation and self-renewal. CHAF1B is overexpressed in several cancers and may represent a potential target for cancer therapy. However, its expression and clinical significance in lung squamous-cell carcinoma (LUSC) remain unclear.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Triple-negative breast cancer (TNBC) is a difficulty and bottleneck in the clinical treatment of breast cancer due to a lack of effective therapeutic targets. Herein, we first report that secernin 2 (SCRN2), an uncharacterized gene in human cancer, acts as a novel tumor suppressor in TNBC to inhibit cancer progression and enhance therapeutic sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition both in vitro and in vivo. SCRN2 is downregulated in TNBC through chaperone-mediated autophagic degradation, and its downregulation is associated with poor patient prognosis.
View Article and Find Full Text PDFEMBO J
January 2025
Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Chromosome segregation relies on kinetochores that assemble on specialized centromeric chromatin containing a histone H3 variant. In budding yeast, a single centromeric nucleosome containing Cse4 assembles at a sequence-defined 125 bp centromere. Yeast centromeric sequences are poor templates for nucleosome formation in vitro, suggesting the existence of mechanisms that specifically stabilize Cse4 nucleosomes in vivo.
View Article and Find Full Text PDFbioRxiv
November 2024
Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
To maintain genome stability, proliferating cells must enact a program of telomere maintenance. While most tumors maintain telomeres through the action of telomerase, a subset of tumors utilize a DNA-templated process termed Alternative Lengthening of Telomeres or ALT. ALT is associated with mutations in the ATRX/DAXX/H3.
View Article and Find Full Text PDFJ Neurochem
January 2025
Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry/Hubei Province of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Brain damage induced by ischemia promotes the development of cognitive dysfunction, thus increasing the risk of dementia such as Alzheimer's disease (AD). Studies indicate that cellular acidification-triggered activation of asparagine endopeptidase (AEP) plays a key role in ischemic brain injury, through multiple molecular pathways, including cleavage of its substrates such as SET (inhibitor 2 of PP2A, I ) and Tau. However, whether direct targeting AEP can effectively prevent post-stroke cognitive impairment (PSCI) remains unanswered.
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