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Status |
Public on Aug 13, 2020 |
Title |
Functional Interplay between Histone H2B ADP-Ribosylation and Phosphorylation Controls Adipogenesis |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Although ADP-ribosylation of histones by PARP-1 has been linked to genotoxic stress responses, its role in physiological processes has remained elusive. We found that ADPribosylation of histone H2B-Glu35 inhibits the differentiation of adipocyte precursors, leading to a reduction of newly formed adipocytes in white adipose tissue. ADP-ribosylation of Glu35 by PARP-1 inhibits phosphorylation of adjacent H2B-Ser36, which is required for the proadipogenic gene expression program. It also inhibits adipogenesis in cultured cells and a mouse lineage tracing genetic model. The activity of PARP-1 on H2B requires NMNAT-1, a nuclear NAD+ synthase, which serves as a specificity factor to direct PARP-1 catalytic activity to Glu and Asp residues. Collectively, our results demonstrate a functional interplay between H2B-Glu35 ADP-ribosylation and H2B-Ser36 phosphorylation that controls adipogenesis and cancer cell proliferation.
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Overall design |
Using RNA-seq in 3T3-L1 cells ectopically expressing Wt or mutant histone H2B during a time course of differentiation.
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Web link |
https://pubmed.ncbi.nlm.nih.gov/32822587/
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Contributor(s) |
Huang D, Camacho CV, Setlem R, Ryu KW, Parameswaran B, Gupta RK, Kraus WL |
Citation(s) |
32822587 |
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Submission date |
Aug 20, 2019 |
Last update date |
Nov 12, 2020 |
Contact name |
W. Lee Kraus |
E-mail(s) |
lee.kraus@utsouthwestern.edu
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Organization name |
UT Southwestern Medical Center
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Street address |
5323 Harry Hines Blvd.
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City |
Dallas |
State/province |
TX |
ZIP/Postal code |
75390-8511 |
Country |
USA |
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Platforms (1) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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Samples (32)
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Relations |
BioProject |
PRJNA561140 |
SRA |
SRP218880 |
Supplementary file |
Size |
Download |
File type/resource |
GSE136055_H3K27me3_ChIP_seq_E35A_H2B_Merged.bw |
59.4 Mb |
(ftp)(http) |
BW |
GSE136055_H3K27me3_ChIP_seq_E35A_H2B_Merged_Input.bw |
61.6 Mb |
(ftp)(http) |
BW |
GSE136055_H3K27me3_ChIP_seq_WT_H2B_Merged.bw |
60.5 Mb |
(ftp)(http) |
BW |
GSE136055_H3K27me3_ChIP_seq_WT_H2B_Merged_Input.bw |
65.6 Mb |
(ftp)(http) |
BW |
GSE136055_cuffdiff_0d_WTvsE35A.diff.gz |
791.9 Kb |
(ftp)(http) |
DIFF |
GSE136055_cuffdiff_0d_WTvsE36A.diff.gz |
829.4 Kb |
(ftp)(http) |
DIFF |
GSE136055_cuffdiff_2d_WTvsE35A.diff.gz |
810.1 Kb |
(ftp)(http) |
DIFF |
GSE136055_cuffdiff_2d_WTvsE36A.diff.gz |
783.5 Kb |
(ftp)(http) |
DIFF |
GSE136055_cuffdiff_4d_WTvsE35A.diff.gz |
828.0 Kb |
(ftp)(http) |
DIFF |
GSE136055_cuffdiff_4d_WTvsE36A.diff.gz |
785.7 Kb |
(ftp)(http) |
DIFF |
GSE136055_cuffdiff_6d_WTvsE35A.diff.gz |
831.2 Kb |
(ftp)(http) |
DIFF |
GSE136055_cuffdiff_6d_WTvsE36A.diff.gz |
790.1 Kb |
(ftp)(http) |
DIFF |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |