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Role of Histone Methyltransferase in Breast Cancer
Published in Meenu Gupta, Rachna Jain, Arun Solanki, Fadi Al-Turjman, Cancer Prediction for Industrial IoT 4.0: A Machine Learning Perspective, 2021
Surekha Manhas, Zaved Ahmed Khan
It has been found that a particular pattern of posttranslational modifications of histones and their crosstalk might designate as a code that determines possible outcomes generated by transcriptional machinery. Among the various distinct histone modification crosstalk pathways, the most studied one is H3K79me3 and H3K4me3 stimulation by H2BK120u1 found in yeast. In addition, another studied pathway is RAD6/BRE1, a ubiquitin ligase that established the H2BK123u1 during the ignition of the transcription process and localized to the transcription initiation site and the gene bodies that are active [35]. RAD6/BRE1 depletion or H2BK123 mutation causes severe critical loss of H3K79me3 and H3K4me3 [36,37]. The positive crosstalk among H2BK123u1, H3K79me3, and H3K4me3 is specific, which does not lead to H3K36me3 regulation designated as another transcriptional hallmark [36,37]. Both modifications lie in close proximity to the exposed surface of the nucleosome, H3K79 and H2BK123 [38]. In yeast DOT1, H3K79 methyltransferase has been observed to be influenced by mutations or deletions of histone residue on the tail portion of H2B histone protein [38]. The situation is converted into a more complex zone in humans because distribution of DOTIL and H3K79me3 is not completely dependant on H2BK120u1. Localization of DOT1L occurs locally at active genes but reaches the maximum to TSS (Transcription Start site) [39]. Moreover, it shows its binding affinity with PoL11 phosphorylated forms, including Ser2 and Ser5 [39]. Moreover, H3K79me3 is recognized as a marker of transcriptionally active genes, but the exact transcriptional mechanism is not discovered yet. In mammals, crosstalk between H2BK120u1 and H3K4me3 mostly remain conserved, as RNF20/40, BRE1 homologs result in the global reduction of H3K4me3 [40]. Recently, a study has been carried out on E3 ligase, MSL1/MSL2, which catalyzes H2BK34u1. The study revealed the crosstalk between H2BK34u1 and H3K4me3 [41]. MLL complex activity stimulates allosterically by H2BK34u1 and H2BK120u1 through binding with the ASH2L subunit [42]. The nucleosome-exposed surface of H2BK34 has ubiquitylation sites that act as a favorable substrate for binding with MLL complex or SET1 [42].
The relationship between histone posttranslational modification and DNA damage signaling and repair
Published in International Journal of Radiation Biology, 2019
Ajit K Sharma, Michael J. Hendzel
H2B ubiquitylation is important for DNA damage checkpoint activation and timely initiation of repair in human cells (Moyal et al. 2011; Nakamura et al. 2011). RNF20/RNF40 dependent H2B monoubiquitylation is needed for recruitment of repair factors in an ATM-dependent manner and is necessary for faithful repair through both pathways, HR and NHEJ in human cells (Moyal et al. 2011; Nakamura et al. 2011). Depletion of RNF20/40 does not affect formation of γH2AX foci but rather their persistence (Moyal et al. 2011). The physiological role of H2B ubiquitylation in the response to DNA damage needs further investigation. A list of histone ubiquitylation sites and their function summarized in Table 4.
RNF20 deletion causes inflammation in model of sepsis through the NLRP3 activation
Published in Immunopharmacology and Immunotoxicology, 2023
Anlong Qi, Yancun Liu, Jianhua Zhai, Yongtao Wang, Wang Li, Tong Wang, Yanfen Chai
In vitro model, over-expression of RNF20 induced VDR mRNA expression at 24 or 48 h of transfection, while down-regulation of RNF20 reduced vitamin D R mRNA at 24 or 48 h of transfection (Figure 5(A and B)). The association between RNF20 and VDR proteins was confirmed by Co-IP (Figure 5(C)). In vitro model, over-expression of RNF20 reduced VDR ubiquitination, while down-regulation of RNF20 increased VDR ubiquitination (Figure 5(D)). Taken together, RNF20 exerted an activating role in sepsis through the suppression of VDR ubiquitination.