SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis.
The mammalian cytoplasmic protein SirT2 is a member of the Sir2 family of NAD+-dependent protein deacetylases involved in caloric restriction-dependent life span extension. We found that SirT2 and its yeast counterpart Hst2 have a strong preference for histone H4K16Ac in their deacetylation activity in vitro and in vivo. We have pinpointed the decrease in global levels of H4K16Ac during the mammalian cell cycle to the G2/M transition that coincides with SirT2 localization on chromatin. Mouse embryonic fibroblasts (MEFs) deficient for SirT2 show higher levels of H4K16Ac in mitosis, in contrast to the normal levels exhibited by SirT1-deficient MEFs. The enzymatic conversion of H4K16Ac to its deacetylated form may be pivotal to the formation of condensed chromatin. Thus, SirT2 is a major contributor to this enzymatic conversion at the time in the cell's life cycle when condensed chromatin must be generated anew.
Vaquero
Alejandro
A
Howard Hughes Medical Institute, Piscataway, NJ 08854, USA.
Scher
Michael B
MB
Lee
Dong Hoon
DH
Sutton
Ann
A
Cheng
Hwei-Ling
HL
Alt
Frederick W
FW
Serrano
Lourdes
L
Sternglanz
Rolf
R
Reinberg
Danny
D
D000818:Animals; D002453:Cell Cycle; D002843:Chromatin / Q000201:enzymology*; D003593:Cytoplasm / Q000201:enzymology; D005347:Fibroblasts / Q000201:enzymology; D006655:Histone Deacetylases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D056565:Sirtuin 2; D037761:Sirtuins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D002843:Chromatin; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; C423033:HST2 protein, S cerevisiae; C474199:SIRT2 protein, human; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases; D008239:Lysine