NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1.
PARP-1 is the most abundantly expressed member of a family of proteins that catalyze the transfer of ADP-ribose units from NAD+ to target proteins. Herein, we describe previously uncharacterized nucleosome binding properties of PARP-1 that promote the formation of compact, transcriptionally repressed chromatin structures. PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. The automodification activity of PARP-1 is potently stimulated by nucleosomes, causing the release of PARP-1 from chromatin. The NAD+-dependent activities of PARP-1 are reversed by PARG, a poly(ADP-ribose) glycohydrolase, and are inhibited by ATP. In vivo, PARP-1 incorporation is associated with transcriptionally repressed chromatin domains that are spatially distinct from both histone H1-repressed domains and actively transcribed regions. Thus, PARP-1 functions both as a structural component of chromatin and a modulator of chromatin structure through its intrinsic enzymatic activity.
Kim
Mi Young
MY
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Mauro
Steven
S
Gévry
Nicolas
N
Lis
John T
JT
Kraus
W Lee
WL
D000255:Adenosine Triphosphate / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D002843:Chromatin; D006657:Histones; D046911:Macromolecular Substances; D009707:Nucleosomes; D011994:Recombinant Proteins; D009243:NAD; D000255:Adenosine Triphosphate; D011065:Poly(ADP-ribose) Polymerases; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase