@article{f8c6e97e01554b2b8f527afbd533cfe0,
title = "Functional Interplay between Histone H2B ADP-Ribosylation and Phosphorylation Controls Adipogenesis",
abstract = "Although ADP-ribosylation of histones by PARP-1 has been linked to genotoxic stress responses, its role in physiological processes and gene expression has remained elusive. We found that NAD+-dependent ADP-ribosylation of histone H2B-Glu35 by small nucleolar RNA (snoRNA)-activated PARP-1 inhibits AMP kinase-mediated phosphorylation of adjacent H2B-Ser36, which is required for the proadipogenic gene expression program. The activity of PARP-1 on H2B requires NMNAT-1, a nuclear NAD+ synthase, which directs PARP-1 catalytic activity to Glu and Asp residues. ADP-ribosylation of Glu35 and the subsequent reduction of H2B-Ser36 phosphorylation inhibits the differentiation of adipocyte precursors in cultured cells. Parp1 knockout in preadipocytes in a mouse lineage-tracing genetic model increases adipogenesis, leading to obesity. Collectively, our results demonstrate a functional interplay between H2B-Glu35 ADP-ribosylation and H2B-Ser36 phosphorylation that controls adipogenesis.",
keywords = "ADP-ribosylation, PARP-1, adipogenesis, differentiation, histones, phosphorylation, proliferation, proteomics, snoRNA",
author = "Dan Huang and Camacho, {Cristel V.} and Rohit Setlem and Ryu, {Keun Woo} and Balaji Parameswaran and Gupta, {Rana K.} and Kraus, {W. Lee}",
note = "Funding Information: The authors would like to thank the following: (1) members of the Kraus lab for continued input and feedback on this project; (2) Laura Banaszynski, Rebecca Gupte, Sridevi Challa, and Daeseok Kim for comments and feedback on this manuscript; (3) Tulip Nandu for assisting with the preliminary mass spectrometry data analysis; (4) Andrew Kelleher for assisting with the immunohistochemistry from mouse tissues; (5) Glen Liszczak for the nucleosomes used in the in vitro PARylation assays; (6) the University of Texas (UT) Southwestern Proteomics Core Facility under the direction of Andrew Lemoff; (7) the UT Southwestern Live Cell Imaging Core Facility under the direction of Kate Luby-Phelps; (8) the UT Southwestern Next Generation Sequencing Core under the direction of Ralf Kittler; and (9) the UT Southwestern Histo Pathology Core. This work was supported by a grant from the National Institutes of Health ( NIH )/ National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) ( R01 DK069710 ) and funds from the Cecil H. and Ida Green Center for Reproductive Biology Sciences Endowment to W.L.K. ",
year = "2020",
month = sep,
day = "17",
doi = "10.1016/j.molcel.2020.08.002",
language = "English (US)",
volume = "79",
pages = "934--949.e14",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",
}