PMC

Types of epigenetic regulators mutated in AML: Epigenetic “writers,” such as DNA methyltransferases, histone methyltransferase (HMT), and histone acetyltransferases (HAT), deposit methylation and/or acetylation on DNA or on histones. These epigenetic marks may be removed by epigenetic “erasers,” including histone demethylase (HDM) and histone deacetylase complexes (HDACs). Epigenetic “readers” are highly specialized proteins that specifically bind to distinct epigenetic marks to convey this information to downstream effectors.

Lead sources in the epigenetic sandstone-hosted Pb-Zn deposit at Laisvall, Sweden. (a) Simplified geological map of Scandinavia showing the location of sandstone-hosted Pb-Zn sulphide deposits in Ediacaran to lower Cambrian autochthonous sandstone and calcite-galena vein occurrences in Palaeoproterozoic crystalline basement close to the current erosional front of the Caledonian orogen. (b) ²⁰⁷Pb/²⁰⁴Pb vs. ²⁰⁶Pb/²⁰⁴Pb plot showing the isotopic composition of (i) Pb-Zn sulphides from the Laisvall deposit (Supplementary Data Table ) and in basement-hosted calcite-galena vein occurrences (Storuman and Åkerlandet districts in Fig. 1a; Supplementary Data Table ), (ii) residue and leachate fractions from granite basement samples from the Laisvall area and their corresponding K-feldspar aliquots (Supplementary Data Table ) (ii) extractable organic matter (EOM) from shale hydrocarbon source rocks of the Alum Shale Formation and from the two mineralized sandstone horizons in the Laisvall deposit (Supplementary Data Table ), (c) Model age of lead source vs. timing of mineralization between 400 and 600 Ma for the Laisvall deposit and the calcite-galena vein occurrences in Palaeoproterozoic basement.

Schematic examples of potential epigenetic therapy targeting ALT and TA in glioma. Left: Inhibitory compounds against histone deacetylase HDAC class I and IIa may affect directly both ALT and TA. Right: The histone chaperones ATRX/DAXX deposit the H3.3 at telomeric chromatin and thereby maintain silencing histone marks such as H3K9me3 and H3K27me3. Demethylase inhibitors block demethylation of H3 with possible change in chromatin structure that may block directly ALT and TA via LINE-1. Symbols as defined in .

a Schematic depiction of various structural domains within the estrogen receptor (ERα). The LBD harbors surfaces for dimerization as well as coactivator binding. Upon binding E2, helix 12 within the LBD shifts to an active conformation, which promotes ERα interaction with coactivators. b Pioneer factors such as FOXA1, GATA3, PBX1, and AP-2γ preferentially bind to hypomethylated genomic sites bearing their respective motifs. Importantly, these sites are often already marked with low levels of H3K4me1/2, which increase with the recruitment of pioneer factors such as FOXA1. Upon stimulation with the E2 ligand, pioneer factors facilitate the localization of liganded ERα to the chromatin. This leads to the activation of gene expression as ERα recruits epigenetic activators such as P300/CBP, the SWI/SNF complex, PRMTs and EZH2 (through direct contact or through coactivators such as SRC-1/2/3 and Mediator) to deposit activating epigenetic marks such as H4R3me1 and H3K27Ac (solid-colored). However, through interactions with corepressors such as LCOR and NCoR1/2, liganded ERα and tamoxifen-bound ERα can also recruit epigenetic repressors including HDACs and the NuRD complex to mediate gene repression by removing active epigenetic marks (faintly colored).