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Review
11 July 2022
Functions and Interactions of Mammalian KDM5 Demethylases
Egor Pavlenko
2 more and 
Simon Poepsel

Mammalian histone demethylases of the KDM5 family are mediators of gene expression dynamics during developmental, cellular differentiation, and other nuclear processes. They belong to the large group of JmjC domain containing, 2-oxoglutarate (2-OG) dependent oxygenases and target methylated lysine 4 of histone H3 (H3K4me1/2/3), an epigenetic mark associated with active transcription. In recent years, KDM5 demethylases have gained increasing attention due to their misregulation in many cancer entities and are intensively explored as therapeutic targets. Despite these implications, the molecular basis of KDM5 function has so far remained only poorly understood. Little is known about mechanisms of nucleosome recognition, the recruitment to genomic targets, as well as the local regulation of demethylase activity. Experimental evidence suggests close physical and functional interactions with epigenetic regulators such as histone deacetylase (HDAC) containing complexes, as well as the retinoblastoma protein (RB). To understand the regulation of KDM5 proteins in the context of chromatin, these interactions have to be taken into account. Here, we review the current state of knowledge on KDM5 function, with a particular emphasis on molecular interactions and their potential implications. We will discuss and outline open questions that need to be addressed to better understand histone demethylation and potential demethylation-independent functions of KDM5s. Addressing these questions will increase our understanding of histone demethylation and allow us to develop strategies to target individual KDM5 enzymes in specific biological and disease contexts.

6,564 views
27 citations
Review
24 June 2022
DNA N6-Methyladenine Modification in Eukaryotic Genome
Hao Li
6 more and 
Yinan Du
Detection methods of 6 mA. (A) 6 mA-IPseq and 6 mA-REseq. (B) HPLC-MS/MS. (C) SMRT. (D) Deep learning predictive model.

DNA methylation is treated as an important epigenetic mark in various biological activities. In the past, a large number of articles focused on 5 mC while lacking attention to N6-methyladenine (6 mA). The presence of 6 mA modification was previously discovered only in prokaryotes. Recently, with the development of detection technologies, 6 mA has been found in several eukaryotes, including protozoans, metazoans, plants, and fungi. The importance of 6 mA in prokaryotes and single-celled eukaryotes has been widely accepted. However, due to the incredibly low density of 6 mA and restrictions on detection technologies, the prevalence of 6 mA and its role in biological processes in eukaryotic organisms are highly debated. In this review, we first summarize the advantages and disadvantages of 6 mA detection methods. Then, we conclude existing reports on the prevalence of 6 mA in eukaryotic organisms. Next, we highlight possible methyltransferases, demethylases, and the recognition proteins of 6 mA. In addition, we summarize the functions of 6 mA in eukaryotes. Last but not least, we summarize our point of view and put forward the problems that need further research.

6,276 views
17 citations
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Frontiers in Epigenetics and Epigenomics

Insights into Epigenomic Landscape: Understanding the Impact of Environmental Factors
Edited by Suresh Kumar, Karishma Seem, Shuo Li
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08 June 2025
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