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Series GSE85100 Query DataSets for GSE85100
Status Public on Jan 23, 2017
Title PARP-1 Controls the Adipogenic Transcriptional Program by PARylating C/EBPβ and Modulating Its Transcriptional Activity
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Poly(ADP-ribosyl)ation (PARylation) is a regulatory post-translational modification of proteins mediated by PARP family members, such as PARP-1. Although PARP-1 and PARylation have been widely studied, very few examples of definitive biological roles for site-specific PARylation of proteins exist in the literature. Here we show that C/EBPβ, a key pro-adipogenic transcription factor, is PARylated by PARP-1 at Glu135, as well as two adjacent amino acids (K133 and E139). PARylation at these sites inhibits C/EBPβ’s DNA binding and transcriptional activities, and attenuates adipogenesis in various cell-based models of adipogenesis. Interestingly, PARP-1 catalytic activity drops precipitously during the first 48 hours of hormone-induced differentiation, corresponding to a release of C/EBPβ from PARylation-mediated inhibition. This allows the binding of C/EBPβ to the promoters of pro-adipogenic target genes (e.g., Cebpa, Pparg2), their subsequent expression, and continued differentiation. In this regard, depletion of PARP-1 or chemical inhibition of its catalytic activity enhances early adipogenic events. Collectively, our results provide a clear example of how site-specific PARylation of a key transcription factor can affect its molecular and biochemical functions, as well as the biological outcomes that it controls.
Overall design ChIP-seq (C/EBP beta) were perfomed in 3T3-L1 cells expressing doxycycline inducible HA tagged C/EBP beta LAP wildtype and PARylation site mutant, with or without doxycycline and PARP inhibitor treatment.
Web link
Contributor(s) Luo X, Ryu KW, Kim D, Nandu T, Kraus LW
Citation(s) 28107648
Submission date Aug 02, 2016
Last update date May 15, 2019
Contact name W. Lee Kraus
Organization name UT Southwestern Medical Center
Street address 5323 Harry Hines Blvd.
City Dallas
State/province TX
ZIP/Postal code 75390-8511
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (20)
GSM2257695 WT_-Dox_rep_1_Input
GSM2257696 WT_-Dox_rep_2_Input
GSM2257697 Mut_-Dox_rep_1_Input
BioProject PRJNA336169
SRA SRP080809

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Supplementary file Size Download File type/resource
GSE85100_Mut_+Dox_CEBPB_ChIP_peaks.bed.gz 258.3 Kb (ftp)(http) BED
GSE85100_Mut_-Dox_CEBPB_ChIP_peaks.bed.gz 101.6 Kb (ftp)(http) BED
GSE85100_WT_+Dox_+BYK_CEBPB_ChIP_peaks.bed.gz 265.5 Kb (ftp)(http) BED
GSE85100_WT_+Dox_CEBPB_ChIP_peaks.bed.gz 180.2 Kb (ftp)(http) BED
GSE85100_WT_-Dox_CEBPB_ChIP_peaks.bed.gz 159.3 Kb (ftp)(http) BED
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