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Figure 3: Scheme representing chromatin accessibility and NRs classical mechanism of action. Chromatin accessibility and histone modifications contribute to NR binding. The N-termini of histones have specific amino acids that are sensitive to posttranslational modifications, which contribute to chromatin status (active or silent). At the top of the scheme (inactive chromatin), there is an example of NRs bound to its RE and associated with transcription corepressor complexes. The presence of histone deacetylases (e.g., HDAC) leads to removal of any chromatin activating histone acetylation sites causing formation of transcriptionally repressed chromatin structure. At the bottom (active chromatin) there is an example of NRs heterodimers bound to the corresponding RE and associated with coactivator complexes. Formation of a coactivator complex induces histone modifications such as acetylation (Ac) by histone acetyltransferases (HAT) and methylation (Me) that in turn alter chromatin structure. This allows for the entry of the basal transcriptional machinery, including RNA pol II and transcription factors (TFs). The complete assembly then leads to the activation of target gene transcription (adapted from [37,38,39]).