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Germ Cell Tumors of the Central Nervous System
Published in David A. Walker, Giorgio Perilongo, Roger E. Taylor, Ian F. Pollack, Brain and Spinal Tumors of Childhood, 2020
Matthew J. Murray, Ute Bartels, James C. Nicholson
JMJD1C, a histone demethylase, is of particular interest to GCT pathogenesis as it is required for long-term maintenance of male germ cells28 and has been shown to epigenetically regulate spermatogenesis through multiple mechanisms.29 Epigenetic mechanisms have also been implicated in GCT development at a number of levels.13 Methylation is one such mechanism and likely contributes to GCT pathogenesis and the different clinical behavior observed between malignant subtypes.30–33 Another study confirmed previous findings relating to JMJD1C and also identified PI3K pathway mutations in CNS GCTs, including in mTOR.8 Germinomas and NGGCTs, as well as CNS and testicular GCTs, showed similar mutational profiles, suggesting a common molecular pathogenesis.8
Inhibition of histone demethylase JMJD1C attenuates cardiac hypertrophy and fibrosis induced by angiotensin II
Published in Journal of Receptors and Signal Transduction, 2020
Shenqian Zhang, Ying Lu, Chenyang Jiang
It is well known that histone modifications play key roles in gene transcription. Over the past decades, a great deal has demonstrated that histone methylation plays a key role in cardiac remodeling [7–9]. In our study, we identified a H3K9me2 and H3K9me1 demethylase JMJD1C involved in cardiac hypertrophy and fibrosis induced by pathological stress. JMJD1C is a global regulator of chromatin remodeling and gene expression. Gene expression is mediated by transcription factors and histone-modifying enzymes. Many different histone-modifying enzymes, including HDACs, HATs, HMTs, and HDMs, contribute to the dynamic regulation of chromatin structure and function, with concomitant impacts on gene transcription [28–30]. Unlike transcription factors that often have on-off effects on gene transcription, the effects of histone-modifying enzymes on gene transcription are often modulatory. This modulatory effect can be context- and gene-dependent such that only those genes exceeded the threshold will yield a phenotype and be identified. In our study, we did not identify what genes were different in JMJD1C knockdown and control cells, and which was regulated by histone methylation change. It will be interesting to identify these genes using RNA-seq and ChIP-seq combined analysis to further investigate the relationship between JMJD1C-regulated H3K9me2 marks which ultimately determines the transcriptional state of the gene as either active, repressed, or poised for activation.
c-MYB and DMTF1 in Cancer
Published in Cancer Investigation, 2019
Elizabeth A. Fry, Kazushi Inoue
Sroczynska et al. (131) used a mouse model of human AML induced by the MLL-AF9 fusion oncogene; they also performed screening with a shRNA library to find novel drug targets. One of the best candidate drug targets identified in these screens was again Jmjd1c. Depletion of JMJD1C impaired the growth and colony formation of mouse MLL-AF9 cells in vitro (131). Depletion of JMJD1C impaired expansion and colony formation of human leukemic cell lines, with the strongest effect observed in the MLL-rearranged ALL cell line. The growth defect upon JMJD1C depletion was caused by increased apoptosis indicating that JMJD1C as a potential therapeutic target for human leukemias (131). Overexpression of c-Myb or c-Myc significantly provided a growth advantage over Jmjd1c-depleted cells, indicating the functional relationship between c-Myb/c-Myc and Jmjd1c in colony formation of leukemic cells (131).