TY - JOUR
T1 - Global SUMOylation on active chromatin is an acute heat stress response restricting transcription
AU - Niskanen, Einari A
AU - Malinen, Marjo
AU - Sutinen, Päivi
AU - Toropainen, Sari
AU - Paakinaho, Ville
AU - Vihervaara, Anniina
AU - Joutsen, Jenny
AU - Kaikkonen, Minna U
AU - Sistonen, Lea
AU - Palvimo, Jorma J
PY - 2015/7/28
Y1 - 2015/7/28
N2 - BACKGROUND: Cells have developed many ways to cope with external stress. One distinctive feature in acute proteotoxic stresses, such as heat shock (HS), is rapid post-translational modification of proteins by SUMOs (small ubiquitin-like modifier proteins; SUMOylation). While many of the SUMO targets are chromatin proteins, there is scarce information on chromatin binding of SUMOylated proteins in HS and the role of chromatin SUMOylation in the regulation of transcription.RESULTS: We mapped HS-induced genome-wide changes in chromatin occupancy of SUMO-2/3-modified proteins in K562 and VCaP cells using ChIP-seq. Chromatin SUMOylation was further correlated with HS-induced global changes in transcription using GRO-seq and RNA polymerase II (Pol2) ChIP-seq along with ENCODE data for K562 cells. HS induced a rapid and massive rearrangement of chromatin SUMOylation pattern: SUMOylation was gained at active promoters and enhancers associated with multiple transcription factors, including heat shock factor 1. Concomitant loss of SUMOylation occurred at inactive intergenic chromatin regions that were associated with CTCF-cohesin complex and SETDB1 methyltransferase complex. In addition, HS triggered a dynamic chromatin binding of SUMO ligase PIAS1, especially onto promoters. The HS-induced SUMOylation on chromatin was most notable at promoters of transcribed genes where it positively correlated with active transcription and Pol2 promoter-proximal pausing. Furthermore, silencing of SUMOylation machinery either by depletion of UBC9 or PIAS1 enhanced expression of HS-induced genes.CONCLUSIONS: HS-triggered SUMOylation targets promoters and enhancers of actively transcribed genes where it restricts the transcriptional activity of the HS-induced genes. PIAS1-mediated promoter SUMOylation is likely to regulate Pol2-associated factors in HS.
AB - BACKGROUND: Cells have developed many ways to cope with external stress. One distinctive feature in acute proteotoxic stresses, such as heat shock (HS), is rapid post-translational modification of proteins by SUMOs (small ubiquitin-like modifier proteins; SUMOylation). While many of the SUMO targets are chromatin proteins, there is scarce information on chromatin binding of SUMOylated proteins in HS and the role of chromatin SUMOylation in the regulation of transcription.RESULTS: We mapped HS-induced genome-wide changes in chromatin occupancy of SUMO-2/3-modified proteins in K562 and VCaP cells using ChIP-seq. Chromatin SUMOylation was further correlated with HS-induced global changes in transcription using GRO-seq and RNA polymerase II (Pol2) ChIP-seq along with ENCODE data for K562 cells. HS induced a rapid and massive rearrangement of chromatin SUMOylation pattern: SUMOylation was gained at active promoters and enhancers associated with multiple transcription factors, including heat shock factor 1. Concomitant loss of SUMOylation occurred at inactive intergenic chromatin regions that were associated with CTCF-cohesin complex and SETDB1 methyltransferase complex. In addition, HS triggered a dynamic chromatin binding of SUMO ligase PIAS1, especially onto promoters. The HS-induced SUMOylation on chromatin was most notable at promoters of transcribed genes where it positively correlated with active transcription and Pol2 promoter-proximal pausing. Furthermore, silencing of SUMOylation machinery either by depletion of UBC9 or PIAS1 enhanced expression of HS-induced genes.CONCLUSIONS: HS-triggered SUMOylation targets promoters and enhancers of actively transcribed genes where it restricts the transcriptional activity of the HS-induced genes. PIAS1-mediated promoter SUMOylation is likely to regulate Pol2-associated factors in HS.
KW - Chromatin/metabolism
KW - DNA-Binding Proteins/physiology
KW - Gene Expression Regulation
KW - Heat Shock Transcription Factors
KW - Heat-Shock Response/genetics
KW - Humans
KW - K562 Cells
KW - Promoter Regions, Genetic
KW - Protein Inhibitors of Activated STAT/metabolism
KW - RNA Polymerase II/metabolism
KW - Small Ubiquitin-Related Modifier Proteins/metabolism
KW - Sumoylation
KW - Transcription Factors/physiology
KW - Transcription, Genetic
U2 - 10.1186/s13059-015-0717-y
DO - 10.1186/s13059-015-0717-y
M3 - Article
C2 - 26259101
SN - 1474-7596
VL - 16
SP - 1
EP - 19
JO - GENOME BIOLOGY
JF - GENOME BIOLOGY
IS - 1
ER -