ADP-ribosylation of H3K27acα by PARP-1 is Required for IFNγ-stimulated Transcriptional Responses in Macrophages [H3K27ac_ChIP-Seq_mutants_iBMDM]
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ABSTRACT: A key determinant of the pro-inflammatory responses in macrophages is the Signal Transducers and Activators of Transcription (STAT) family member, H3K27acα. H3K27acα activation by interferon-gamma (IFNγ) leads to induction of a transcriptional program that is coordinated in a large part by post-translational modifications such as phosphorylation. Poly(ADP-ribose) Polymerases (PARPs), which include PARP-1, catalyze the addition of ADP-ribose moieties (ADP-ribosylation) to target proteins and modulate their function. We found that PARP-1 mediates IFNγ-stimulated transcription by regulating genome-wide binding of H3K27acα and its IFNγ-dependent phosphorylation. We identified H3K27acα as a target of PARP-1 and found sites of ADP-ribosylation on its DNA-binding (DBD) and Transcription Activation (TA) domains. Surprisingly, ADP-ribosylation on the DBD and TA domains had distinct functional consequences on H3K27acα transcriptional activity. Moreover, loss of ADP-ribosylation on either site led to diminished pro-inflammatory responses. These results suggest that PARP-1-driven ADP-ribosylation of H3K27acα is a critical mediator of inflammation in macrophages.
ORGANISM(S): Mus musculus
PROVIDER: GSE147954 | GEO | 2021/05/13
REPOSITORIES: GEO
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