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Histone modification pathways. Histone acetylation is mediated by HAT and deacetylation is catalyzed by the HDAC family. The upper row represents histone acetylation/deacetylation processes mediated by classic HDAC family members, including classes I, II and IV. Histone acetylation causes an open chromatin structure, leading to active transcription, whereas histone deacetylation is always associated with transcriptional repression. The middle row indicates a class III HDAC family member, SIRT1, which deacetylates both histone and protein substrates, resulting in gene silencing in most cases. The lower row represents histone methylation as another important histone modification. Histone methylation is mediated by HMT, and either gene activation or gene repression by histone methylation is dependent upon the particular lysine residue that is modified. HAT, histone acetyltransferase; HDAC, histone deacetylase; HMT, histone methyltransferase. SIRT1, Sirtuin (silent mating type information regulation 2 homolog) 1.

Histone modification pathways. Histone acetylation is mediated by HAT and deacetylation is catalyzed by the HDAC family. The upper row represents histone acetylation/deacetylation processes mediated by classic HDAC family members, including classes I, II and IV. Histone acetylation causes an open chromatin structure, leading to active transcription, whereas histone deacetylation is always associated with transcriptional repression. The middle row indicates a class III HDAC family member, SIRT1, which deacetylates both histone and protein substrates, resulting in gene silencing in most cases. The lower row represents histone methylation as another important histone modification. Histone methylation is mediated by HMT, and either gene activation or gene repression by histone methylation is dependent upon the particular lysine residue that is modified. HAT, histone acetyltransferase; HDAC, histone deacetylase; HMT, histone methyltransferase. SIRT1, Sirtuin (silent mating type information regulation 2 homolog) 1.

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The molecular mechanisms of aging are the subject of much research and have facilitated potential interventions to delay aging and aging-related degenerative diseases in humans. The aging process is frequently affected by environmental factors, and caloric restriction is by far the most effective and established environmental manipulation for exten...

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... DNA strand producing a compact chromatin state that is associated with transcriptional repression. By contrast, the modification of histone acetylation removes the positive charge and results in an open chromatin structure, which leads to active transcription ( Figure 2). ...
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... acetylation and deacetylation processes are cata- lyzed by specific enzymes called histone acetyltrans- ferases (HATs) and HDACs, respectively [71,72] (Figure 2 In addition to their deacetylation function, HDACs are believed to participate in the regulation of many cellular functions and gene expression through interactions with hundreds of different transcription factors [71,73]. It has also been reported that HDAC activity is increased dur- ing CR, suggesting that global deacetylation may be a protective mechanism against nutrition stress and may influence the aging processes [31]. ...
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... yeast, Sir2-mediated deacetylation of histones H3 and H4 and concomitant silencing of protein recruit- ment occurs specifically in heterochromatic regions located at extrachromosomal ribosomal DNA, telomeres and silenced mating-type loci, which benefit lifespan extension in yeast [33,57,83,95]. Human SIRT1 estab- lishes and maintains chromatin silencing by preferential deacetylation at histone H4 lysine 16 (H4K16), but it also has been shown to deacetylate the loci of histone H3 lysine 9 (H3K9) in vitro [96] (Figure 2). Further, SIRT1 affects the levels of histone methylation by deace- tylation of SUV39H1, a mammalian histone methyl- transferase suppressor, leading to increased levels of the trimethylated H3K9 (H3K9Me3) modification (a chro- matin repressor) [97,98]. ...
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... classed as a HDAC, SIRT1 deacetylates a broad range of substrates, including many nonhistone substrates [33,83] (Table 2 and Figure 2). These poten- tial substrates may include several key transcription fac- tors and regulatory proteins that are involved in multiple pathways linked to physiological and metabolic processes that contribute to lifespan extension by CR (Table 2 and Figure 1). ...
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... histone acetylation, histone methylation is another important histone modification that regulates gene expression [72] (Figure 2). In contrast to histone acetylation, which is always associated with open chro- matin status and subsequent gene activation, differen- tially methylated forms of histones show unique association patterns with specific proteins that recognize these markers and thus lead to gene silencing or activat- ing effects. ...

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