Chemical genetic discovery of PARP targets reveals a role for PARP-1 in transcription elongation.

Poly[adenosine diphosphate (ADP)-ribose] polymerases (PARPs) are a family of enzymes that modulate diverse biological processes through covalent transfer of ADP-ribose from the oxidized form of nicotinamide adenine dinucleotide (NAD(+)) onto substrate proteins. Here we report a robust NAD(+) analog-sensitive approach for PARPs, which allows PARP-specific ADP-ribosylation of substrates that is suitable for subsequent copper-catalyzed azide-alkyne cycloaddition reactions. Using this approach, we mapped hundreds of sites of ADP-ribosylation for PARPs 1, 2, and 3 across the proteome, as well as thousands of PARP-1-mediated ADP-ribosylation sites across the genome.

The histone variant MacroH2A1 regulates target gene expression in part by recruiting the transcriptional coregulator PELP1.

MacroH2A1 is a histone variant harboring an ∼25-kDa carboxyl-terminal macrodomain. Due to its enrichment on the inactive X chromosome, macroH2A1 was thought to play a role in transcriptional repression. However, recent studies have shown that macroH2A1 occupies autosomal chromatin and regulates genes in a context-specific manner.