In eukaryotic cells, gene expressions on chromosome DNA are orchestrated by a dynamic chromosome structure state that is largely controlled by chromatin-regulating proteins, which regulate chromatin structures, release DNA from the nucleosome, and activate or suppress gene expression by modifying nucleosome histones or mobilizing DNA-histone structure. The two classes of chromatin- regulating proteins are 1) enzymes that modify histones through methylation, acetylation, phosphorylation, adenosine diphosphate–ribosylation, glycosylation, sumoylation, or ubiquitylation and 2) enzymes that remodel DNA-histone structure with energy from ATP hydrolysis. Chromatin-regulating proteins, which modulate DNA-histone interaction, change chromatin conformation, and increase or decrease the binding of functional DNA regulating protein complexes, have major functions in nuclear processes, including gene transcription and DNA replication, repair, and recombination.
In contrast to histone modifications, which do not require energy, chromatin remodeling is an energy-driven process in which chromatin remodelers use the energy of ATP hydrolysis to change the nucleosome structure. Chromatin remodelers have two types of effects on chromatin dynamics: 1) they package genomic DNA, and incorporate histones into the nucleosome, or 2) release DNA from the histones. After DNA replication, chromatin remodelers pack genomic DNA into nucleosomes. During DNA repair, DNA replication, and gene transcription, chromatin remodelers move or eject histones from nucleosomes. These molecular processes are accomplished through an orchestrated conformation change that involves the DNA-binding and the translocation domains of chromatin remodelers. All chromatin remodelers share similar DNA-dependent ATPase domains and domains that interact with histone modifications, nucleosomes, and other transcription factors.
Chromatin Remodeler Functions
The mechanism by which chromatin remodelers slide DNA around the nucleosome is not quite clear. Current studies support a model in which the DNA binding domain and translocation domain of chromatin remodelers concertedly change their conformation and move DNA to form a loose loop around the nucleosome. The ATPase domains of chromatin remodelers share high homology with known DNA translocases and have been proven to function in DNA translocation events. In this way, chromatin remodelers disrupt DNA–histone interaction, and the histone octamer can be ejected, replaced, or restructured. Chromatin remodelers are involved in DNA repair, replication, transcription, and recombination and in chromosome assembly. On the basis of their interaction with chromatin, chromatin remodelers can be classified as having one of two functions: 1) evicting or replacing histones to open chromatin to DNA or 2) inserting or spacing histones to restructure or assemble chromatin.
Chromatin Remodeler Families
The SWI/SNF (SW Itching defect / Sucrose NonFermenting) chromatin remodeler consists of 8-14 protein subunits. Although this chromatin remodeling family is involved in disrupting the interaction between genomic DNA and histones to slide, eject, or insert histones, SWI/SNF chromatin remodelers have no role in packaging or assembling chromatin.
Figure 1. Structure of Snf2 ATPase bound to a nucleosome.
The ISWI (Simulated SWItch) chromatin remodeling body consists of 2 or 8 subunit proteins with specific catalytic domains. Human cells have eight different ISWI chromatin remodeling complexes, which are b-WICH, WICH, NoRC, RSF, ACF, CHRAC, CERF and NURF.
The CHD (Chromodomain, Helicase, DNA binding) chromatin remodeling device can be divided into two groups, CHD and NuRD (nuclear small-weight plastic and deacetylase), which have 1 and 10 subunits, respectively. In human cells, the catalytic subunits of CHD chromatin remodeling are CHD1, CHD2, CHD6, CHD7, CHD8 and CHD9, while the core ATPase subunits of NuRD chromatin remodeling are Mi-2a / CHD3 and Mi-2b/CHD4.
INO80 chromatin remodeling has three different protein complexes (INO80, SRCAP and TIP60/p400), each complex containing approximately 10 subunits. The core ATPase in these complexes is INO80. SRCAP and p400, they also have histone acetyltransferase activity.
1. Pollock R E.; et al. An Overview of Chromatin-Regulating Proteins in Cells. Current Protein & Peptide Science, 2016, 17(5):401-410.