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The histone demethylase KDM5C enhances the sensitivity of acute myeloid leukemia cells to lenalidomide by stabilizing cereblon.

Cell Mol Biol Lett

January 2025

Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Key Laboratory of Drug Research for Prevention and Treatment of Hyperlipidemic Diseases, Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, China.

Background: The protein cereblon (CRBN) mediates the antileukemia effect of lenalidomide (Len). Len binds to CRBN, recruits IKZF1/IKZF3, and promotes their ubiquitination and degradation, through which Len exhibits its antileukemia and antimyeloma activity. Therefore, the protein level of CRBN might affect the antiproliferative effect of Len.

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In Arabidopsis (Arabidopsis thaliana), light and circadian clock signaling converge on PHYTOCHROME-INTERACTING FACTORS (PIFs) 4 and 5 to produce a daily rhythm of hypocotyl elongation. PIF4 and PIF5 expression is repressed at dusk by the evening complex (EC), consisting of EARLY FLOWERING3 (ELF3), ELF4, and LUX ARRHYTHMO (LUX). Here, we report that ELF3 recruits the JUMONJI (JMJ) H3K4me3 demethylases JMJ17 and JMJ18 to the PIF4 and PIF5 loci in the evening to remove their H3K4me3 marks.

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Motivation: Histone modifications play an important role in transcription regulation. Although the general importance of some histone modifications for transcription regulation has been previously established, the relevance of others and their interaction is subject to ongoing research. By training Machine Learning models to predict a gene's expression and explaining their decision making process, we can get hints on how histone modifications affect transcription.

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Mammalian J-domain protein DNAJC9 interacts with histones H3-H4 and is important for cell proliferation. However, its exact function remains unclear. Here, we show that, in the fission yeast Schizosaccharomyces pombe, loss of Djc9, the ortholog of DNAJC9, renders the histone chaperone Asf1 no longer essential for growth.

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Epstein-Barr virus (EBV) contributes to ~1.5% of human cancers, including lymphomas, gastric and nasopharyngeal carcinomas. In most of these, nearly 80 viral lytic genes are silenced by incompletely understood epigenetic mechanisms, precluding use of antiviral agents such as ganciclovir to treat the 200,000 EBV-associated cancers/year.

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