The epigenetic regulation of cell cycle and chromatin dynamic by sirtuins

摘要: The chromatin consists of a hierarchical and dynamical structure that is modulated during the different cell cycle stages in order to maintain genome integrity preserve genetic information coded DNA. dynamic depends on coordination remodeling processes: histone modifications, enzymes/complexes, DNA methylation architectural proteins (CAPs). Within chromatin, histone-mediated regulation responds mainly modification its N-terminal domain or "tail." Among acetylation at specific lysine residues (K) one best characterized, 16 H4 most frequently acetylated residue eukaryotes. form H4K16 an important mark actively transcribed euchromatin from yeast humans; whereas non associated with gene silencing heterochromatin regions. this governed by three enzymes: acetyltransferases (HAT) MOF (males absent first), deacetylases (HDAC) SIRT1 SIRT2. Therefore, both groups enzymes are essential for expression organization nucleus, regulating transition between transcriptionally active inactive state chromatin. SIRT2 belong Class III HDACs, termed as sirtuins, which crucial genomic integrity, adaptation environment aging, among other functions. On hand, only mammalian sirtuin located cytoplasm, known shuttle nucleus G2/M. Consistently, HDAC has main role deacetylating H4K16Ac G2-M. So far, mitosis been demonstrated culture experiments studies. first time, our study demonstrates levels vivo. As matter fact, results support function involvement control not levels, but also H4K20me1-3 whole cycle. Notwithstanding, happens members, shown regulate deacetylate non-histone substrates govern cycle, stress response, survival stability. Furthermore, roles modulating progression found diverse mitotic checkpoint such CDH1, CDC20, BubR1 p53. Additionally, suggest Abstract patterns generated attend two complementary mechanisms: deacetylation PR-Set7, monomethyltrasferase H4K20. We have clearly involved H4K20me1 deposition under stressful conditions, integrity. heterochomatin formation substrates. In maintenance due marks (H3K9Ac H1K26Ac) related HP1, Suv39h1 Ezh2. addition, deacetylates H4K16Ac, H3K9Ac H1K26Ac promoters expression; regulates p53, FoxO factors, Rb, others, specifically modulate pattern. Nonetheless, recently implicated throughout Mcm10, eukaryotic initiation factor S-phase progression. Accordingly, demonstrate how may be PR-Set7 Suv4-20h2, charge mono- di-methylate H4K20, respectively. Altogether evidences sirtuins preserving dynamics S-phase.