Box 2 Chromatin remodeler complexes

Chromatin remodeling controls access of various transcription factors and other relevant proteins to our DNA and has a crucial regulatory function enabled and maintained by at least for subfamilies of helicases: the switch/sucrose non-fermentable (SWI/SNF), the chromodomain helicase DNA-binding (CHD) family, the imitation switch (ISWI), and the inositol requiring 80 (INO80 complex) [66, 67]. All act by organizing and editing nucleosomes through ATP hydrolysis, rendering the DNA more or less accessible for transcription factors. In humans, and higher eukaryotes in general, the composition of each of these complexes is dynamic and may differ slightly depending on the cell type and developmental stage. During neural development, the SWI/SNF complex and the CHD family of chromatin remodelers are most active

The CHD family contains nine proteins, CHD1-9, each presenting with chromodomains. The family is divided in three subgroups. The first group, CHD1 and 2, has a C-terminal DNA-binding domain. The second group, CHD3 and 4, has N-terminal zinc fingers, and the last group, CHD 5–9, contains several domains including a DNA-binding domain, CR-domains, and SANT domains. This family of proteins can be part of a larger complex but can also act as a remodeler independently of other proteins. The proteins in this family are, for instance, involved in neural crest cell migration and synapse formation

The SWI/SNF complex (referred to as the BAF complex in mammals) contains 15 subunits with the core ATPase subunit consisting of either BRG1 (SMARCA4) or BRM (SMARCA2). The BAF complex can both inhibit and activate gene transcription, thereby playing an important role in the development of different tissues, especially in the neural system. The complex has been found to be important for neural progenitor proliferation, dendritic outgrowth, and axonal development

The ISWI family can form multiple small remodeler complexes. The ATPase subunit can be SMARCA1 or SMARCA5, of which SMARCA5 is the most abundant. The ISWI family is, like the other remodelers, important for nucleosome positioning and thus for regulating transcription and generate higher-order chromatin. Additionally, this family was also found to be important in the DNA damage response and thus for DNA repair [68, 69]

The last family of chromatin remodelers is the INO80 complex, containing 15 subunits, forming three different modules. Only two of these modules are necessary for INO80 to perform nucleosome remodeling. They contain the two domains, Snf2-like ATPase/helicase and helicase-SANT-associated/Post-HAS, essential for ATP-dependent nucleosome remodeling [70]. Besides nucleosome remodeling and thus regulating transcription, the INO80 complex is also important for DNA repair and replication and exchanging histones [71]