Abstract
PARP-1 is an abundant nuclear enzyme that regulates gene expression, although the underlying mechanisms are unclear. We examined the interplay between PARP-1, histone 3 lysine 4 trimethylation (H3K4me3), and linker histone H1 in the chromatin-dependent control of transcription. We show that PARP-1 is required for a series of molecular outcomes at the promoters of PARP-1-regulated genes, leading to a permissive chromatin environment that allows loading of the RNA Pol II machinery. PARP-1 does so by (1) preventing demethylation of H3K4me3 through the PARylation, inhibition, and exclusion of the histone demethylase KDM5B; and (2) promoting the exclusion of H1 and the opening of promoter chromatin. Upon depletion of PARP-1, these outcomes do not occur efficiently. Interestingly, cellular signaling pathways can use the regulated depletion of PARP-1 to modulate these chromatin-related molecular outcomes. Collectively, our results help to elucidate the roles of PARP-1 in the regulation of chromatin structure and transcription.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 736-749 |
| Number of pages | 14 |
| Journal | Molecular Cell |
| Volume | 39 |
| Issue number | 5 |
| DOIs | |
| State | Published - Sep 2010 |
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Keywords
- DNA
- Proteins
- Signaling
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
- Medicine(all)
Cite this
PARP-1 Regulates Chromatin Structure and Transcription through a KDM5B-Dependent Pathway. / Krishnakumar, Raga; Kraus, W. Lee.
In: Molecular Cell, Vol. 39, No. 5, 09.2010, p. 736-749.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - PARP-1 Regulates Chromatin Structure and Transcription through a KDM5B-Dependent Pathway
AU - Krishnakumar, Raga
AU - Kraus, W. Lee
PY - 2010/9
Y1 - 2010/9
N2 - PARP-1 is an abundant nuclear enzyme that regulates gene expression, although the underlying mechanisms are unclear. We examined the interplay between PARP-1, histone 3 lysine 4 trimethylation (H3K4me3), and linker histone H1 in the chromatin-dependent control of transcription. We show that PARP-1 is required for a series of molecular outcomes at the promoters of PARP-1-regulated genes, leading to a permissive chromatin environment that allows loading of the RNA Pol II machinery. PARP-1 does so by (1) preventing demethylation of H3K4me3 through the PARylation, inhibition, and exclusion of the histone demethylase KDM5B; and (2) promoting the exclusion of H1 and the opening of promoter chromatin. Upon depletion of PARP-1, these outcomes do not occur efficiently. Interestingly, cellular signaling pathways can use the regulated depletion of PARP-1 to modulate these chromatin-related molecular outcomes. Collectively, our results help to elucidate the roles of PARP-1 in the regulation of chromatin structure and transcription.
AB - PARP-1 is an abundant nuclear enzyme that regulates gene expression, although the underlying mechanisms are unclear. We examined the interplay between PARP-1, histone 3 lysine 4 trimethylation (H3K4me3), and linker histone H1 in the chromatin-dependent control of transcription. We show that PARP-1 is required for a series of molecular outcomes at the promoters of PARP-1-regulated genes, leading to a permissive chromatin environment that allows loading of the RNA Pol II machinery. PARP-1 does so by (1) preventing demethylation of H3K4me3 through the PARylation, inhibition, and exclusion of the histone demethylase KDM5B; and (2) promoting the exclusion of H1 and the opening of promoter chromatin. Upon depletion of PARP-1, these outcomes do not occur efficiently. Interestingly, cellular signaling pathways can use the regulated depletion of PARP-1 to modulate these chromatin-related molecular outcomes. Collectively, our results help to elucidate the roles of PARP-1 in the regulation of chromatin structure and transcription.
KW - DNA
KW - Proteins
KW - Signaling
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U2 - 10.1016/j.molcel.2010.08.014
DO - 10.1016/j.molcel.2010.08.014
M3 - Article
VL - 39
SP - 736
EP - 749
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 5
ER -