[
Epigenetics,
2009]
Distinct chromatin remodeling complexes can share a common ATPase subunit. The functional characteristics of each remodeling complex are determined by the respective ATPase-associated subunits. The Mi-2 nucleosome remodeling ATPase has so far only been shown to reside within Nucleosome Remodeling and Deacetylase (NuRD) complexes. Here we will review the recent discovery of two Mi-2 related remodelers that function independently of NuRD and that act as SUMO (small ubiquitin-related modifier)-dependent corepressors: First, Mi-2 exists in a novel chromatin remodeling complex, dMec, that does not rely on histone deacetylation to effect transcriptional repression of proneural genes. Second, the Mi-2 related factor dCHD3 acts as a monomer and does not associate with additional subunits in vivo. These recent results have uncovered an unanticipated complexity in the composition and function of CHD (Chromodomain-Helicase-DNA-binding) complexes.
[
Exp Gerontol,
2012]
Aging represents a triple threat for myocardial infarction (MI). Not only does the incidence of MI increase with age, but the heart becomes more susceptible to MI induced damage and protective interventions such as ischemic preconditioning (IPC) become less effective. Therefore, any rational therapeutic strategy must be built around the ability to combat the detrimental effects of ischemia in aged individuals. To accomplish this, we need to develop a better understanding of how ischemic damage, protection, and aging are linked. In this regard, mitochondria have emerged as a common theme. First, mitochondria contribute to cell damage during ischemia-reperfusion (IR) and are central to cell death. Second, the protective signaling pathways activated by IPC converge on mitochondria, and the opening of mitochondrial ion channels alone is sufficient to elicit protection. Finally, mitochondria clearly influence the aging process, and specific defects in mitochondrial activity are associated with age-related functional decline. This review will summarize the effects of aging on myocardial IR injury and discuss relevant and emerging strategies to protect against MI with an emphasis on mitochondrial function.
[
Curr Top Microbiol Immunol,
2003]
ATP-dependent nucleosome remodeling and core histone tail modifications play important roles in chromatin function. Purification and characterization of the NuRD/Mi-2 complex, which possesses both nucleosome remodeling and histone deacetylase activities, suggests that ATP-dependent nucleosome remodeling and histone tail modification can be coupled. Recent studies indicate that NuRD is an integral part of the MeCP1 complex, suggesting that nucleosome remodeling and histone deacetylation play important roles in methylated DNA silencing. Studies in Caenorhabditis elegans have revealed important functions of the NuRD complex in embryonic patterning and Ras signaling. Accumulating evidence indicates that NuRD may regulate transcription of specific genes by interacting with specific transcriptional factors. In addition, it may also participate in genome-wide transcriptional regulation through an association with histone tails.