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Fig. 1 | Cell & Bioscience

Fig. 1

From: Small molecule modulators of chromatin remodeling: from neurodevelopment to neurodegeneration

Fig. 1

Summary of regulatory mechanisms and the small-molecule drug regulation of chromatin remodeling. Chromatin remodeling involves a dynamic interchange of chromatin between a condensed state (heterochromatin) and a more relaxed state (euchromatin). The underlying mechanisms can be divided into two categories: (1) covalent modification of chromatin components. Epigenetic modifications to histone proteins include but are not limited to acetylation, methylation, phosphorylation and ubiquitination. Enzymes involved include histone acetyltransferase (HAT), histone deacetylase (HDAC), histone methyltransferase (HMT), histone demethylase (HDM), phosphokinase (PK), and phosphatase (PP); DNA methylation is controlled by DNA methyltransferase (DNMT) and DNA demethylase. (2) noncovalent modifications by ATP-dependent CRCs, including the SWI/SNF, ISWI, CHD, and INO80 families. The domain structures of each subfamily of chromatin remodelers are shown. They all contain a conserved ATPase domain, which consists of DEXDc and HELICc domains, thus allowing them to use the energy released from ATP hydrolysis to reposition nucleosomes. Each subfamily member has distinct auxiliary domains and exhibits different modes of nucleosome remodeling (adapted from [46], as detailed in the main text). In addition, some representative small-molecule inhibitors of chromatin remodeling factors are listed. Most of them have been approved for cancer treatment, but in recent years, they have also entered the clinical stage to treat neurodegenerative diseases, as detailed in the last section

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