title: Histone acetyltransferase-1 regulates integrity of cytosolic histone H3-H4 containing complex.
abstract: Amounts of soluble histones in cells are tightly regulated to ensure supplying them for the newly synthesized DNA and preventing the toxic effect of excess histones. Prior to incorporation into chromatin, newly synthesized histones H3 and H4 are highly acetylated in pre-deposition complex, wherein H4 is di-acetylated at Lys-5 and Lys-12 residues by histone acetyltransferase-1 (Hat1), but their role in histone metabolism is still unclear. Here, using chicken DT 40 cytosolic extracts, we found that histones H3/H4 and their chaperone Asf1, including RbAp48, a regulatory subunit of Hat1 enzyme, were associated with Hat1. Interestingly, in HAT1-deficient cells, cytosolic histones H3/H4 fractions on sucrose gradient centrifugation, having a sedimentation coefficient of 5-6S in DT40 cells, were shifted to lower molecular mass fractions, with Asf1. Further, sucrose gradient fractionation of semi-purified tagged Asf1-complexes showed the presence of Hat1, RbAp48 and histones H3/H4 at 5-6S fractions in the complexes. These findings suggest the possible involvement of Hat1 in regulating cytosolic H3/H4 pool mediated by Asf1-containing cytosolic H3/H4 pre-deposition complex.
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, 8200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Hirak Kumar
authors.initials: HK
authors.lastname: Barman
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Takami
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishijima
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Shibahara
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Sanematsu
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002384:Catalysis; D002645:Chickens / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism*; D018832:Molecular Chaperones
chemical_list: D006657:Histones; D018832:Molecular Chaperones; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C110880:histone acetyltransferase type B complex