Mono-methylation of lysine 27 at histone 3 confers lifelong susceptibility to stress

Angélica Torres-Berrío; Molly Estill; Vishwendra Patel; Aarthi Ramakrishnan; Hope Kronman; Angélica Minier-Toribio; Orna Issler; Caleb J. Browne; Eric M. Parise; Yentl Y. van der Zee; Deena M. Walker; Freddyson J. Martínez-Rivera; Casey K. Lardner; Romain Durand-de Cuttoli; Scott J. Russo; Li Shen; Simone Sidoli; Eric J. Nestler

doi:10.1016/j.neuron.2024.06.006

Mono-methylation of lysine 27 at histone 3 confers lifelong susceptibility to stress

Angélica Torres-Berrío, Molly Estill, Vishwendra Patel, Aarthi Ramakrishnan, Hope Kronman, Angélica Minier-Toribio, Orna Issler, Caleb J. Browne, Eric M. Parise, Yentl Y. van der Zee, Deena M. Walker, Freddyson J. Martínez-Rivera, Casey K. Lardner, Romain Durand-de Cuttoli, Scott J. Russo, Li Shen, Simone Sidoli, Eric J. Nestler

Biochemistry

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Histone post-translational modifications are critical for mediating persistent alterations in gene expression. By combining unbiased proteomics profiling and genome-wide approaches, we uncovered a role for mono-methylation of lysine 27 at histone H3 (H3K27me1) in the enduring effects of stress. Specifically, mice susceptible to early life stress (ELS) or chronic social defeat stress (CSDS) displayed increased H3K27me1 enrichment in the nucleus accumbens (NAc), a key brain-reward region. Stress-induced H3K27me1 accumulation occurred at genes that control neuronal excitability and was mediated by the VEFS domain of SUZ12, a core subunit of the polycomb repressive complex-2, which controls H3K27 methylation patterns. Viral VEFS expression changed the transcriptional profile of the NAc, led to social, emotional, and cognitive abnormalities, and altered excitability and synaptic transmission of NAc D1-medium spiny neurons. Together, we describe a novel function of H3K27me1 in the brain and demonstrate its role as a “chromatin scar” that mediates lifelong stress susceptibility.

Original language	English (US)
Journal	Neuron
DOIs	https://doi.org/10.1016/j.neuron.2024.06.006
State	Accepted/In press - 2024

Keywords

H3K27me1
SUZ12
depression
early life stress
histone modifications
medium spiny neurons
nucleus accumbens
polycomb repressive complex 2

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2024.06.006

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Torres-Berrío, A., Estill, M., Patel, V., Ramakrishnan, A., Kronman, H., Minier-Toribio, A., Issler, O., Browne, C. J., Parise, E. M., van der Zee, Y. Y., Walker, D. M., Martínez-Rivera, F. J., Lardner, C. K., Durand-de Cuttoli, R., Russo, S. J., Shen, L., Sidoli, S., & Nestler, E. J. (Accepted/In press). Mono-methylation of lysine 27 at histone 3 confers lifelong susceptibility to stress. Neuron. https://doi.org/10.1016/j.neuron.2024.06.006

Torres-Berrío, A, Estill, M, Patel, V, Ramakrishnan, A, Kronman, H, Minier-Toribio, A, Issler, O, Browne, CJ, Parise, EM, van der Zee, YY, Walker, DM, Martínez-Rivera, FJ, Lardner, CK, Durand-de Cuttoli, R, Russo, SJ, Shen, L, Sidoli, S & Nestler, EJ 2024, 'Mono-methylation of lysine 27 at histone 3 confers lifelong susceptibility to stress', Neuron. https://doi.org/10.1016/j.neuron.2024.06.006

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abstract = "Histone post-translational modifications are critical for mediating persistent alterations in gene expression. By combining unbiased proteomics profiling and genome-wide approaches, we uncovered a role for mono-methylation of lysine 27 at histone H3 (H3K27me1) in the enduring effects of stress. Specifically, mice susceptible to early life stress (ELS) or chronic social defeat stress (CSDS) displayed increased H3K27me1 enrichment in the nucleus accumbens (NAc), a key brain-reward region. Stress-induced H3K27me1 accumulation occurred at genes that control neuronal excitability and was mediated by the VEFS domain of SUZ12, a core subunit of the polycomb repressive complex-2, which controls H3K27 methylation patterns. Viral VEFS expression changed the transcriptional profile of the NAc, led to social, emotional, and cognitive abnormalities, and altered excitability and synaptic transmission of NAc D1-medium spiny neurons. Together, we describe a novel function of H3K27me1 in the brain and demonstrate its role as a “chromatin scar” that mediates lifelong stress susceptibility.",

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year = "2024",

doi = "10.1016/j.neuron.2024.06.006",

language = "English (US)",

journal = "Neuron",

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AU - Torres-Berrío, Angélica

AU - Estill, Molly

AU - Patel, Vishwendra

AU - Ramakrishnan, Aarthi

AU - Kronman, Hope

AU - Minier-Toribio, Angélica

AU - Issler, Orna

AU - Browne, Caleb J.

AU - Parise, Eric M.

AU - van der Zee, Yentl Y.

AU - Walker, Deena M.

AU - Martínez-Rivera, Freddyson J.

AU - Lardner, Casey K.

AU - Durand-de Cuttoli, Romain

AU - Russo, Scott J.

AU - Shen, Li

AU - Sidoli, Simone

AU - Nestler, Eric J.

PY - 2024

Y1 - 2024

N2 - Histone post-translational modifications are critical for mediating persistent alterations in gene expression. By combining unbiased proteomics profiling and genome-wide approaches, we uncovered a role for mono-methylation of lysine 27 at histone H3 (H3K27me1) in the enduring effects of stress. Specifically, mice susceptible to early life stress (ELS) or chronic social defeat stress (CSDS) displayed increased H3K27me1 enrichment in the nucleus accumbens (NAc), a key brain-reward region. Stress-induced H3K27me1 accumulation occurred at genes that control neuronal excitability and was mediated by the VEFS domain of SUZ12, a core subunit of the polycomb repressive complex-2, which controls H3K27 methylation patterns. Viral VEFS expression changed the transcriptional profile of the NAc, led to social, emotional, and cognitive abnormalities, and altered excitability and synaptic transmission of NAc D1-medium spiny neurons. Together, we describe a novel function of H3K27me1 in the brain and demonstrate its role as a “chromatin scar” that mediates lifelong stress susceptibility.

AB - Histone post-translational modifications are critical for mediating persistent alterations in gene expression. By combining unbiased proteomics profiling and genome-wide approaches, we uncovered a role for mono-methylation of lysine 27 at histone H3 (H3K27me1) in the enduring effects of stress. Specifically, mice susceptible to early life stress (ELS) or chronic social defeat stress (CSDS) displayed increased H3K27me1 enrichment in the nucleus accumbens (NAc), a key brain-reward region. Stress-induced H3K27me1 accumulation occurred at genes that control neuronal excitability and was mediated by the VEFS domain of SUZ12, a core subunit of the polycomb repressive complex-2, which controls H3K27 methylation patterns. Viral VEFS expression changed the transcriptional profile of the NAc, led to social, emotional, and cognitive abnormalities, and altered excitability and synaptic transmission of NAc D1-medium spiny neurons. Together, we describe a novel function of H3K27me1 in the brain and demonstrate its role as a “chromatin scar” that mediates lifelong stress susceptibility.

KW - H3K27me1

KW - SUZ12

KW - depression

KW - early life stress

KW - histone modifications

KW - medium spiny neurons

KW - nucleus accumbens

KW - polycomb repressive complex 2

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SN - 0896-6273

JO - Neuron

JF - Neuron

ER -

Mono-methylation of lysine 27 at histone 3 confers lifelong susceptibility to stress

Abstract

Keywords

ASJC Scopus subject areas

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