Details

Autor(en) / Beteiligte

• Nusinow, Dmitri A.
• Hernández-Muñoz, Inmaculada
• Fazzio, Thomas G.
• Shah, Girish M.
• Kraus, W. Lee
• Panning, Barbara

Titel

Poly(ADP-ribose) Polymerase 1 Is Inhibited by a Histone H2A Variant, MacroH2A, and Contributes to Silencing of the Inactive X Chromosome

Ist Teil von

• The Journal of biological chemistry, 2007-04, Vol.282 (17), p.12851-12859

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2007

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that is involved in modulating chromatin structure, regulation of gene expression, and sensing DNA damage. Here, we report that PARP-1 enzymatic activity is inhibited by macroH2A, a vertebrate histone H2A variant that is enriched on facultative heterochromatin. MacroH2A family members have a large C-terminal non-histone domain (NHD) and H2A-like histone domain. MacroH2A1.2 and PARP-1 interact in vivo and in vitro via the NHD. The NHD of each macroH2A family member was sufficient to inhibit PARP-1 enzymatic activity in vitro. The NHD of macroH2A1.2 was a mixed inhibitor of PARP-1 catalytic activity, with affects on both catalytic activity and the substrate binding affinity of PARP-1. Depletion of PARP-1 by RNA interference caused reactivation of a reporter gene on the inactive X chromosome, demonstrating that PARP-1 participates in the maintenance of silencing. These results suggest that one function of macroH2A in gene silencing is to inhibit PARP-1 enzymatic activity, and this may affect PARP-1 association with chromatin.