Oscillatory cAMP signaling rapidly alters H3K4 methylation

Huff, Tyler C.; Camarena, Vladimir; Sant, David W.; Wilkes, Zachary; Van Booven, Derek; Aron, Allegra T.; Muir, Ryan K.; Renslo, Adam R.; Chang, Christopher J.; Monje, Paula V.; Wang, Gaofeng

doi:10.26508/lsa.201900529

Title: Oscillatory cAMP signaling rapidly alters H3K4 methylation

Journal Article · Fri Dec 27 00:00:00 EST 2019 · Life Science Alliance

DOI:https://doi.org/10.26508/lsa.201900529· OSTI ID:1603588

Huff, Tyler C. ^[1];

^[1]; Sant, David W. ^[1]; Wilkes, Zachary ^[1]; Van Booven, Derek ^[1]; Aron, Allegra T. ^[2]; Muir, Ryan K. ^[3];

^[3]; Chang, Christopher J. ^[2]; Monje, Paula V. ^[4];

^[1]

Univ. of Miami Miller School of Medicine, Miami, FL, USA
Univ. of California, Berkeley, CA (United States)
Univ. of California, San Francisco, CA (United States)
Indiana Univ. School of Medicine, Indianapolis, IN (United States)

Epigenetic variation reflects the impact of a dynamic environment on chromatin. However, it remains elusive how environmental factors influence epigenetic events. Here, we show that G protein–coupled receptors (GPCRs) alter H3K4 methylation via oscillatory intracellular cAMP. Activation of Gs-coupled receptors caused a rapid decrease of H3K4me3 by elevating cAMP, whereas stimulation of Gi-coupled receptors increased H3K4me3 by diminishing cAMP. H3K4me3 gradually recovered towards baseline levels after the removal of GPCR ligands, indicating that H3K4me3 oscillates in tandem with GPCR activation. cAMP increased intracellular labile Fe(II), the cofactor for histone demethylases, through a non-canonical cAMP target—Rap guanine nucleotide exchange factor-2 (RapGEF2), which subsequently enhanced endosome acidification and Fe(II) release from the endosome via vacuolar H⁺-ATPase assembly. Removing Fe(III) from the media blocked intracellular Fe(II) elevation after stimulation of Gs-coupled receptors. Iron chelators and inhibition of KDM5 demethylases abolished cAMP-mediated H3K4me3 demethylation. Taken together, these results suggest a novel function of cAMP signaling in modulating histone demethylation through labile Fe(II).

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH)

Grant/Contract Number:: AC02-05CH11231; R01NS089525; GM079465; 339576; T32 GM066698

OSTI ID:: 1603588

Journal Information:: Life Science Alliance, Vol. 3, Issue 1; ISSN 2575-1077

Publisher:: Cold Spring Harbor Laboratory PressCopyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 4 works

Citation information provided by
Web of Science

References (49)

Histone Methylation Dynamics and Gene Regulation Occur through the Sensing of One-Carbon Metabolism Mentch, Samantha J.; Mehrmohamadi, Mahya; Huang, Lei Cell Metabolism, Vol. 22, Issue 5 https://doi.org/10.1016/j.cmet.2015.08.024	journal	November 2015
Histone demethylation by a family of JmjC domain-containing proteins Tsukada, Yu-ichi; Fang, Jia; Erdjument-Bromage, Hediye Nature, Vol. 439, Issue 7078 https://doi.org/10.1038/nature04433	journal	December 2005
Rapgef2 Connects GPCR-Mediated cAMP Signals to ERK Activation in Neuronal and Endocrine Cells Emery, A. C.; Eiden, M. V.; Mustafa, T. Science Signaling, Vol. 6, Issue 281 https://doi.org/10.1126/scisignal.2003993	journal	June 2013
Site-specific human histone H3 methylation stability: fast K4me3 turnover Zheng, Yupeng; Tipton, Jeremiah D.; Thomas, Paul M. PROTEOMICS, Vol. 14, Issue 19 https://doi.org/10.1002/pmic.201400060	journal	July 2014
Model-based Analysis of ChIP-Seq (MACS) Zhang, Yong; Liu, Tao; Meyer, Clifford A. Genome Biology, Vol. 9, Issue 9 https://doi.org/10.1186/gb-2008-9-9-r137	journal	January 2008
Inflammasomes in carcinogenesis and anticancer immune responses Zitvogel, Laurence; Kepp, Oliver; Galluzzi, Lorenzo Nature Immunology, Vol. 13, Issue 4 https://doi.org/10.1038/ni.2224	journal	March 2012
Active genes are tri-methylated at K4 of histone H3 Santos-Rosa, Helena; Schneider, Robert; Bannister, Andrew J. Nature, Vol. 419, Issue 6905 https://doi.org/10.1038/nature01080	journal	September 2002
JmjC-domain-containing proteins and histone demethylation Klose, Robert J.; Kallin, Eric M.; Zhang, Yi Nature Reviews Genetics, Vol. 7, Issue 9 https://doi.org/10.1038/nrg1945	journal	September 2006
Calcitonin gene-related peptide promotes Schwann cell proliferation. Cheng, L.; Khan, M.; Mudge, A. W. The Journal of Cell Biology, Vol. 129, Issue 3 https://doi.org/10.1083/jcb.129.3.789	journal	May 1995
edgeR: a Bioconductor package for differential expression analysis of digital gene expression data Robinson, M. D.; McCarthy, D. J.; Smyth, G. K. Bioinformatics, Vol. 26, Issue 1 https://doi.org/10.1093/bioinformatics/btp616	journal	November 2009
HTSeq--a Python framework to work with high-throughput sequencing data Anders, S.; Pyl, P. T.; Huber, W. Bioinformatics, Vol. 31, Issue 2 https://doi.org/10.1093/bioinformatics/btu638	journal	September 2014
Fast and accurate short read alignment with Burrows-Wheeler transform Li, H.; Durbin, R. Bioinformatics, Vol. 25, Issue 14 https://doi.org/10.1093/bioinformatics/btp324	journal	May 2009
The vacuolar (H+)-ATPases — nature's most versatile proton pumps Nishi, Tsuyoshi; Forgac, Michael Nature Reviews Molecular Cell Biology, Vol. 3, Issue 2 https://doi.org/10.1038/nrm729	journal	February 2002
On the Biological Role of Cyclic AMP Sutherland, Earl W. JAMA: The Journal of the American Medical Association, Vol. 214, Issue 7 https://doi.org/10.1001/jama.1970.03180070047009	journal	November 1970
Lysophosphatidic acid (LPA) and its receptor, LPA ₁ , influence embryonic schwann cell migration, myelination, and cell-to-axon segregation: LPA ₁ Regulates Schwann Cell Physiology Anliker, Brigitte; Choi, Ji Woong; Lin, Mu-En Glia, Vol. 61, Issue 12 https://doi.org/10.1002/glia.22572	journal	September 2013
The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation Brier, Ann-Sofie B.; Loft, Anne; Madsen, Jesper G. S. Nucleic Acids Research, Vol. 45, Issue 4 https://doi.org/10.1093/nar/gkw1156	journal	November 2016
Iron uptake and metabolism in the new millennium Dunn, Louise L.; Rahmanto, Yohan Suryo; Richardson, Des R. Trends in Cell Biology, Vol. 17, Issue 2 https://doi.org/10.1016/j.tcb.2006.12.003	journal	February 2007
Regulating gene transcription in response to cyclic AMP elevation Sands, William A.; Palmer, Timothy M. Cellular Signalling, Vol. 20, Issue 3 https://doi.org/10.1016/j.cellsig.2007.10.005	journal	March 2008
Fiji: an open-source platform for biological-image analysis Schindelin, Johannes; Arganda-Carreras, Ignacio; Frise, Erwin Nature Methods, Vol. 9, Issue 7 https://doi.org/10.1038/nmeth.2019	journal	June 2012
Complexity and Diversity of Mammalian Adenylyl Cyclases Sunahara, R. K.; Dessauer, C. W.; Gilman, A. G. Annual Review of Pharmacology and Toxicology, Vol. 36, Issue 1 https://doi.org/10.1146/annurev.pa.36.040196.002333	journal	April 1996
A Chromatin Landmark and Transcription Initiation at Most Promoters in Human Cells Guenther, Matthew G.; Levine, Stuart S.; Boyer, Laurie A. Cell, Vol. 130, Issue 1 https://doi.org/10.1016/j.cell.2007.05.042	journal	July 2007
Epac: Defining a New Mechanism for cAMP Action Gloerich, Martijn; Bos, Johannes L. Annual Review of Pharmacology and Toxicology, Vol. 50, Issue 1 https://doi.org/10.1146/annurev.pharmtox.010909.105714	journal	February 2010
Methionine metabolism influences genomic architecture and gene expression through H3K4me3 peak width Dai, Ziwei; Mentch, Samantha J.; Gao, Xia Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-04426-y	journal	May 2018
Regulation of iron acquisition and storage: consequences for iron-linked disorders De Domenico, Ivana; McVey Ward, Diane; Kaplan, Jerry Nature Reviews Molecular Cell Biology, Vol. 9, Issue 1 https://doi.org/10.1038/nrm2295	journal	January 2008
Quantification of cAMP and cGMP analogs in intact cells: pitfalls in enzyme immunoassays for cyclic nucleotides Werner, Katharina; Schwede, Frank; Genieser, Hans-Gottfried Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 384, Issue 2 https://doi.org/10.1007/s00210-011-0662-6	journal	June 2011
Reading, writing and editing methylated lysines on histone tails: new insights from recent structural studies Justin, Neil; De Marco, Valeria; Aasland, Rein Current Opinion in Structural Biology, Vol. 20, Issue 6 https://doi.org/10.1016/j.sbi.2010.09.012	journal	December 2010
Modulation of gene expression dynamics by co-transcriptional histone methylations Woo, Hyeonju; Dam Ha, So; Lee, Sung Bae Experimental & Molecular Medicine, Vol. 49, Issue 4 https://doi.org/10.1038/emm.2017.19	journal	April 2017
Measuring reproducibility of high-throughput experiments Li, Qunhua; Brown, James B.; Huang, Haiyan The Annals of Applied Statistics, Vol. 5, Issue 3 https://doi.org/10.1214/11-aoas466	journal	September 2011
Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome Heintzman, Nathaniel D.; Stuart, Rhona K.; Hon, Gary Nature Genetics, Vol. 39, Issue 3 https://doi.org/10.1038/ng1966	journal	February 2007
Transcriptional Regulation by Cyclic amp Montminy, Marc Annual Review of Biochemistry, Vol. 66, Issue 1 https://doi.org/10.1146/annurev.biochem.66.1.807	journal	June 1997
The Sequence Alignment/Map format and SAMtools Li, H.; Handsaker, B.; Wysoker, A. Bioinformatics, Vol. 25, Issue 16 https://doi.org/10.1093/bioinformatics/btp352	journal	June 2009
NCS-Rapgef2, the Protein Product of the Neuronal Rapgef2 Gene, Is a Specific Activator of D1 Dopamine Receptor-Dependent ERK Phosphorylation in Mouse Brain Jiang, Sunny Zhihong; Xu, Wenqin; Emery, Andrew C. eneuro, Vol. 4, Issue 5 https://doi.org/10.1523/eneuro.0248-17.2017	journal	September 2017
An Endoperoxide Reactivity-Based FRET Probe for Ratiometric Fluorescence Imaging of Labile Iron Pools in Living Cells Aron, Allegra T.; Loehr, Morten O.; Bogena, Jana Journal of the American Chemical Society, Vol. 138, Issue 43 https://doi.org/10.1021/jacs.6b08016	journal	October 2016
cAMP signaling regulates DNA hydroxymethylation by augmenting the intracellular labile ferrous iron pool Camarena, Vladimir; Sant, David W.; Huff, Tyler C. eLife, Vol. 6 https://doi.org/10.7554/elife.29750	journal	December 2017
Oscillations of cyclic AMP in hormone-stimulated insulin-secreting β-cells Dyachok, Oleg; Isakov, Yegor; Sågetorp, Jenny Nature, Vol. 439, Issue 7074 https://doi.org/10.1038/nature04410	journal	January 2006
Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1 Tahiliani, M.; Koh, K. P.; Shen, Y. Science, Vol. 324, Issue 5929 https://doi.org/10.1126/science.1170116	journal	April 2009
Cyclic AMP compartments and signaling specificity: Role of cyclic nucleotide phosphodiesterases Conti, Marco; Mika, Delphine; Richter, Wito The Journal of General Physiology, Vol. 143, Issue 1 https://doi.org/10.1085/jgp.201311083	journal	December 2013
On the biological role of cyclic AMP Sutherland, E. W. JAMA: The Journal of the American Medical Association, Vol. 214, Issue 7 https://doi.org/10.1001/jama.214.7.1281	journal	November 1970
Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist Parisi, Giulia; Saco, Justin D.; Salazar, Felix B. Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-019-12901-3	journal	January 2020
Quantification of cAMP and cGMP analogs in intact cells: pitfals in enzyme immunoassays for cyclic nucleotides Werner, Katharina; Schwede, Frank; Genieser, Hans-Gottfried BMC Pharmacology, Vol. 11, Issue S1 https://doi.org/10.1186/1471-2210-11-s1-p75	journal	August 2011
seqQscorer: automated quality control of next-generation sequencing data using machine learning Albrecht, Steffen; Sprang, Maximilian; Andrade-Navarro, Miguel A. Genome Biology, Vol. 22, Issue 1 https://doi.org/10.1186/s13059-021-02294-2	journal	March 2021
Measuring reproducibility of high-throughput experiments Li, Qunhua; Brown, James B.; Huang, Haiyan arXiv https://doi.org/10.48550/arxiv.1110.4705	text	January 2011
A reactivity-based probe of the intracellular labile ferrous iron pool Spangler, Benjamin; Morgan, Charles W.; Fontaine, Shaun D. Nature Chemical Biology, Vol. 12, Issue 9 https://doi.org/10.1038/nchembio.2116	journal	July 2016
Histone methylation: a dynamic mark in health, disease and inheritance Greer, Eric L.; Shi, Yang Nature Reviews Genetics, Vol. 13, Issue 5 https://doi.org/10.1038/nrg3173	journal	April 2012
Targeted A-to-G base editing of chloroplast DNA in plants Mok, Young Geun; Hong, Sunghyun; Bae, Su-Ji Nature Plants, Vol. 8, Issue 12 https://doi.org/10.1038/s41477-022-01279-8	journal	December 2022
Targeting redox metabolism: the perfect storm induced by acrylamide poisoning in the brain Raldúa, Demetrio; Casado, Marta; Prats, Eva Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-019-57142-y	journal	January 2020
Involvement of the Nonhomologous Region of Subunit A of the Yeast V-ATPase in Coupling and in Vivo Dissociation Shao, Elim; Forgac, Michael Journal of Biological Chemistry, Vol. 279, Issue 47 https://doi.org/10.1074/jbc.m408278200	journal	September 2004
Glucose starvation increases V-ATPase assembly and activity in mammalian cells through AMP kinase and phosphatidylinositide 3-kinase/Akt signaling McGuire, Christina M.; Forgac, Michael Journal of Biological Chemistry, Vol. 293, Issue 23 https://doi.org/10.1074/jbc.ra117.001327	journal	March 2018
Seven transmembrane receptors: something old, something new Lefkowitz, R. J. Acta Physiologica, Vol. 190, Issue 1 https://doi.org/10.1111/j.1365-201x.2007.01693.x	journal	May 2007

Similar Records

KDM5 histone demethylases repress immune response via suppression of STING

Journal Article · Mon Aug 06 00:00:00 EDT 2018 · PLoS Biology (Online) · OSTI ID:1603588

Wu, Lizhen; Cao, Jian; Cai, Wesley L.; +22 more

The flexible loop L1 of the H3K4 demethylase JARID1B ARID domain has a crucial role in DNA-binding activity

Journal Article · Fri May 28 00:00:00 EDT 2010 · Biochemical and Biophysical Research Communications · OSTI ID:1603588

Yao, Wenming; Peng, Yu; Lin, Donghai

Expression of orphan G-protein coupled receptor GPR174 in CHO cells induced morphological changes and proliferation delay via increasing intracellular cAMP

Journal Article · Fri Jan 04 00:00:00 EST 2013 · Biochemical and Biophysical Research Communications · OSTI ID:1603588

Sugita, Kazuya; Yamamura, Chiaki; Tabata, Ken-ichi; +1 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
cell biology
chromatin & epigenetics

Title: Oscillatory cAMP signaling rapidly alters H3K4 methylation

Citation Formats

References (49)

Similar Records

Related Subjects