Histone Demethylase PHF2 Activates CREB and Promotes Memory Consolidation

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2019 Jul 31

PMID 31359606

Citations 18

Authors

Hye-Jin Kim

Sung Won Hur

Jun Bum Park

Jieun Seo

Jae Jin Shin

Seon-Young Kim

Myoung-Hwan Kim

Do Hyun Han

Jong-Wan Park

Joo Min Park

Sang Jeong Kim

Yang-Sook Chun

Affiliations

Soon will be listed here.

Abstract

Long-term memory formation is attributed to experience-dependent gene expression. Dynamic changes in histone methylation are essential for the epigenetic regulation of memory consolidation-related genes. Here, we demonstrate that the plant homeodomain finger protein 2 (PHF2) histone demethylase is upregulated in the mouse hippocampus during the experience phase and plays an essential role in memory formation. PHF2 promotes the expression of memory-related genes by epigenetically reinforcing the TrkB-CREB signaling pathway. In behavioral tests, memory formation is enhanced by transgenic overexpression of PHF2 in mice, but is impaired by silencing PHF2 in the hippocampus. Electrophysiological studies reveal that PHF2 elevates field excitatory postsynaptic potential (fEPSP) and NMDA receptor-mediated evoked excitatory postsynaptic current (EPSC) in CA1 pyramidal neurons, suggesting that PHF2 promotes long-term potentiation. This study provides insight into the epigenetic regulation of learning and memory formation, which advances our knowledge to improve memory in patients with degenerative brain diseases.

Citing Articles

Gene Expression of Neurogenesis Related to Exercise Intensity in a Cerebral Infarction Rat Model.

Song M, Jo H, Kim E, Kim J, Lee S Int J Mol Sci. 2024; 25(16).

PMID: 39201683 PMC: 11354542. DOI: 10.3390/ijms25168997.

Pharmacogenetics in IBS: update and impact of GWAS studies in drug targets and metabolism.

Camilleri M, Jencks K Expert Opin Drug Metab Toxicol. 2024; 20(5):319-332.

PMID: 38785066 PMC: 11139426. DOI: 10.1080/17425255.2024.2349716.

PHF2 regulates sarcomeric gene transcription in myogenesis.

Fukushima T, Hasegawa Y, Kuse S, Fujioka T, Nikawa T, Masubuchi S PLoS One. 2024; 19(5):e0301690.

PMID: 38701072 PMC: 11068198. DOI: 10.1371/journal.pone.0301690.

Myosin Va-dependent Transport of NMDA Receptors in Hippocampal Neurons.

Gong R, Qin L, Chen L, Wang N, Bao Y, Lu W Neurosci Bull. 2024; 40(8):1053-1075.

PMID: 38291290 PMC: 11306496. DOI: 10.1007/s12264-023-01174-y.

Palmitoylation-driven PHF2 ubiquitination remodels lipid metabolism through the SREBP1c axis in hepatocellular carcinoma.

Do-Won Jeong , Park J, Kim K, Kim J, Huh J, Seo J Nat Commun. 2023; 14(1):6370.

PMID: 37828054 PMC: 10570296. DOI: 10.1038/s41467-023-42170-0.

References

Matynia A, Kushner S, Silva A . Genetic approaches to molecular and cellular cognition: a focus on LTP and learning and memory. Annu Rev Genet. 2002; 36:687-720. DOI: 10.1146/annurev.genet.36.062802.091007. View

Silva A, Kogan J, Frankland P, Kida S . CREB and memory. Annu Rev Neurosci. 1998; 21:127-48. DOI: 10.1146/annurev.neuro.21.1.127. View

Li Q, Zou J, Wang M, Ding X, Chepelev I, Zhou X . Critical role of histone demethylase Jmjd3 in the regulation of CD4+ T-cell differentiation. Nat Commun. 2014; 5:5780. PMC: 4274750. DOI: 10.1038/ncomms6780. View

Baba A, Ohtake F, Okuno Y, Yokota K, Okada M, Imai Y . PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B. Nat Cell Biol. 2011; 13(6):668-75. DOI: 10.1038/ncb2228. View

Barco A, Alarcon J, Kandel E . Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture. Cell. 2002; 108(5):689-703. DOI: 10.1016/s0092-8674(02)00657-8. View

Wu G, Deisseroth K, Tsien R . Activity-dependent CREB phosphorylation: convergence of a fast, sensitive calmodulin kinase pathway and a slow, less sensitive mitogen-activated protein kinase pathway. Proc Natl Acad Sci U S A. 2001; 98(5):2808-13. PMC: 30221. DOI: 10.1073/pnas.051634198. View

Kim H, Hur S, Park J, Seo J, Shin J, Kim S . Histone demethylase PHF2 activates CREB and promotes memory consolidation. EMBO Rep. 2019; 20(9):e45907. PMC: 6726911. DOI: 10.15252/embr.201845907. View

Persengiev S, Green M . The role of ATF/CREB family members in cell growth, survival and apoptosis. Apoptosis. 2003; 8(3):225-8. DOI: 10.1023/a:1023633704132. View

DAVIS H, Squire L . Protein synthesis and memory: a review. Psychol Bull. 1984; 96(3):518-59. View

10.

Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai L . Recovery of learning and memory is associated with chromatin remodelling. Nature. 2007; 447(7141):178-82. DOI: 10.1038/nature05772. View

11.

Kim H, Park J, Lee K, Yoon H, Shin D, Ju U . Plant homeodomain finger protein 2 promotes bone formation by demethylating and activating Runx2 for osteoblast differentiation. Cell Res. 2014; 24(10):1231-49. PMC: 4185351. DOI: 10.1038/cr.2014.127. View

12.

Bambah-Mukku D, Travaglia A, Chen D, Pollonini G, Alberini C . A positive autoregulatory BDNF feedback loop via C/EBPβ mediates hippocampal memory consolidation. J Neurosci. 2014; 34(37):12547-59. PMC: 4160783. DOI: 10.1523/JNEUROSCI.0324-14.2014. View

13.

Sen N, Snyder S . Neurotrophin-mediated degradation of histone methyltransferase by S-nitrosylation cascade regulates neuronal differentiation. Proc Natl Acad Sci U S A. 2011; 108(50):20178-83. PMC: 3250167. DOI: 10.1073/pnas.1117820108. View

14.

Okuno Y, Ohtake F, Igarashi K, Kanno J, Matsumoto T, Takada I . Epigenetic regulation of adipogenesis by PHF2 histone demethylase. Diabetes. 2013; 62(5):1426-34. PMC: 3636657. DOI: 10.2337/db12-0628. View

15.

Federman N, Fustinana M, Romano A . Histone acetylation is recruited in consolidation as a molecular feature of stronger memories. Learn Mem. 2009; 16(10):600-6. DOI: 10.1101/lm.1537009. View

16.

Islam O, Loo T, Heese K . Brain-derived neurotrophic factor (BDNF) has proliferative effects on neural stem cells through the truncated TRK-B receptor, MAP kinase, AKT, and STAT-3 signaling pathways. Curr Neurovasc Res. 2009; 6(1):42-53. DOI: 10.2174/156720209787466028. View

17.

Nakayama J, Rice J, Strahl B, Allis C, Grewal S . Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science. 2001; 292(5514):110-3. DOI: 10.1126/science.1060118. View

18.

Routtenberg A, Rekart J . Post-translational protein modification as the substrate for long-lasting memory. Trends Neurosci. 2005; 28(1):12-9. DOI: 10.1016/j.tins.2004.11.006. View

19.

Bozon B, Kelly A, Josselyn S, Silva A, Davis S, Laroche S . MAPK, CREB and zif268 are all required for the consolidation of recognition memory. Philos Trans R Soc Lond B Biol Sci. 2003; 358(1432):805-14. PMC: 1693143. DOI: 10.1098/rstb.2002.1224. View

20.

Kida S, Josselyn S, Pena de Ortiz S, Kogan J, Chevere I, Masushige S . CREB required for the stability of new and reactivated fear memories. Nat Neurosci. 2002; 5(4):348-55. DOI: 10.1038/nn819. View