Gene Regulation and Systems Biology

The dynamic chromatin activities of Mi-2/Nucleosome Remodeling and Histone deacetylation (Mi-2/NuRD) complexes in mammals are at the basis of current research on stemness, longevity/ageing, and cancer (4-2-1/SLAC), and have been widely studied over the past decade in mammals and the elegant model organism, Caenorhabditis elegans. Interestingly, a common emergent theme from these studies is that of distinct coregulator-recruited Mi-2/NuRD complexes largely orchestrating the 4-2-1/SLAC within a unique paradigm by maintaining genome stability via DNA repair and controlling three types of transcriptional programs in concert in a number of cellular, tissue, and organism contexts. Thus, the core Mi-2/NuRD complex plays a central role in 4-2-1/SLAC. The plasticity and robustness of 4-2-1/SLAC can be interpreted as modulation of specific coregulator(s) within cell-specific, tissue-specific, stage-specific, or organism-specific niches during stress induction, ie, a functional module and its networking, thereby conferring differential responses to different environmental cues. According to “Occam’s razor”, a simple theory is preferable to a complex one, so this simplified notion might be useful for exploring 4-2-1/SLAC with a holistic view. This thought could also be valuable in forming strategies for future research, and could open up avenues for cancer prevention and antiageing strategies.