Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription

Vincenzo Di Cerbo, Fabio Mohn, Daniel P. Ryan, Emilie Montellier, Salim Kacem, Philipp Tropberger, Eleni Kallis, Monika Holzner, Leslie Hoerner, Angelika Feldmann, Florian Martin Richter, Andrew J. Bannister, Gerhard Mittler, Jens Michaelis, Saadi Khochbin, Robert Feil, Dirk Schuebeler, Tom Owen-Hughes, Sylvain Daujat (Lead / Corresponding author), Robert Schneider (Lead / Corresponding author)

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    Abstract

    Post-translational modifications of proteins have emerged as a major mechanism for regulating gene expression. However, our understanding of how histone modifications directly affect chromatin function remains limited. In this study, we investigate acetylation of histone H3 at lysine 64 (H3K64ac), a previously uncharacterized acetylation on the lateral surface of the histone octamer. We show that H3K64ac regulates nucleosome stability and facilitates nucleosome eviction and hence gene expression in vivo. In line with this, we demonstrate that H3K64ac is enriched in vivo at the transcriptional start sites of active genes and it defines transcriptionally active chromatin. Moreover, we find that the p300 co-activator acetylates H3K64, and consistent with a transcriptional activation function, H3K64ac opposes its repressive counterpart H3K64me3. Our findings reveal an important role for a histone modification within the nucleosome core as a regulator of chromatin function and they demonstrate that lateral surface modifications can define functionally opposing chromatin states. DOI: http://dx.doi.org/10.7554/eLife.01632.001.

    Original languageEnglish
    Article numbere01632
    JournaleLife
    Volume3
    DOIs
    Publication statusPublished - 25 Mar 2014

    Fingerprint

    Acetylation
    Nucleosomes
    Transcription
    Histones
    Lysine
    Chromatin
    Histone Code
    Gene expression
    Gene Expression
    Post Translational Protein Processing
    Transcriptional Activation
    Surface treatment
    Catalytic Domain
    Genes
    Chemical activation
    Proteins

    Cite this

    Di Cerbo, V., Mohn, F., Ryan, D. P., Montellier, E., Kacem, S., Tropberger, P., ... Schneider, R. (2014). Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription. eLife, 3, [e01632]. https://doi.org/10.7554/eLife.01632
    Di Cerbo, Vincenzo ; Mohn, Fabio ; Ryan, Daniel P. ; Montellier, Emilie ; Kacem, Salim ; Tropberger, Philipp ; Kallis, Eleni ; Holzner, Monika ; Hoerner, Leslie ; Feldmann, Angelika ; Richter, Florian Martin ; Bannister, Andrew J. ; Mittler, Gerhard ; Michaelis, Jens ; Khochbin, Saadi ; Feil, Robert ; Schuebeler, Dirk ; Owen-Hughes, Tom ; Daujat, Sylvain ; Schneider, Robert. / Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription. In: eLife. 2014 ; Vol. 3.
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    title = "Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription",
    abstract = "Post-translational modifications of proteins have emerged as a major mechanism for regulating gene expression. However, our understanding of how histone modifications directly affect chromatin function remains limited. In this study, we investigate acetylation of histone H3 at lysine 64 (H3K64ac), a previously uncharacterized acetylation on the lateral surface of the histone octamer. We show that H3K64ac regulates nucleosome stability and facilitates nucleosome eviction and hence gene expression in vivo. In line with this, we demonstrate that H3K64ac is enriched in vivo at the transcriptional start sites of active genes and it defines transcriptionally active chromatin. Moreover, we find that the p300 co-activator acetylates H3K64, and consistent with a transcriptional activation function, H3K64ac opposes its repressive counterpart H3K64me3. Our findings reveal an important role for a histone modification within the nucleosome core as a regulator of chromatin function and they demonstrate that lateral surface modifications can define functionally opposing chromatin states. DOI: http://dx.doi.org/10.7554/eLife.01632.001.",
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    Di Cerbo, V, Mohn, F, Ryan, DP, Montellier, E, Kacem, S, Tropberger, P, Kallis, E, Holzner, M, Hoerner, L, Feldmann, A, Richter, FM, Bannister, AJ, Mittler, G, Michaelis, J, Khochbin, S, Feil, R, Schuebeler, D, Owen-Hughes, T, Daujat, S & Schneider, R 2014, 'Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription', eLife, vol. 3, e01632. https://doi.org/10.7554/eLife.01632

    Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription. / Di Cerbo, Vincenzo; Mohn, Fabio; Ryan, Daniel P.; Montellier, Emilie; Kacem, Salim; Tropberger, Philipp; Kallis, Eleni; Holzner, Monika; Hoerner, Leslie; Feldmann, Angelika; Richter, Florian Martin; Bannister, Andrew J.; Mittler, Gerhard; Michaelis, Jens; Khochbin, Saadi; Feil, Robert; Schuebeler, Dirk; Owen-Hughes, Tom; Daujat, Sylvain (Lead / Corresponding author); Schneider, Robert (Lead / Corresponding author).

    In: eLife, Vol. 3, e01632, 25.03.2014.

    Research output: Contribution to journalArticle

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    T1 - Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription

    AU - Di Cerbo, Vincenzo

    AU - Mohn, Fabio

    AU - Ryan, Daniel P.

    AU - Montellier, Emilie

    AU - Kacem, Salim

    AU - Tropberger, Philipp

    AU - Kallis, Eleni

    AU - Holzner, Monika

    AU - Hoerner, Leslie

    AU - Feldmann, Angelika

    AU - Richter, Florian Martin

    AU - Bannister, Andrew J.

    AU - Mittler, Gerhard

    AU - Michaelis, Jens

    AU - Khochbin, Saadi

    AU - Feil, Robert

    AU - Schuebeler, Dirk

    AU - Owen-Hughes, Tom

    AU - Daujat, Sylvain

    AU - Schneider, Robert

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    N2 - Post-translational modifications of proteins have emerged as a major mechanism for regulating gene expression. However, our understanding of how histone modifications directly affect chromatin function remains limited. In this study, we investigate acetylation of histone H3 at lysine 64 (H3K64ac), a previously uncharacterized acetylation on the lateral surface of the histone octamer. We show that H3K64ac regulates nucleosome stability and facilitates nucleosome eviction and hence gene expression in vivo. In line with this, we demonstrate that H3K64ac is enriched in vivo at the transcriptional start sites of active genes and it defines transcriptionally active chromatin. Moreover, we find that the p300 co-activator acetylates H3K64, and consistent with a transcriptional activation function, H3K64ac opposes its repressive counterpart H3K64me3. Our findings reveal an important role for a histone modification within the nucleosome core as a regulator of chromatin function and they demonstrate that lateral surface modifications can define functionally opposing chromatin states. DOI: http://dx.doi.org/10.7554/eLife.01632.001.

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    Di Cerbo V, Mohn F, Ryan DP, Montellier E, Kacem S, Tropberger P et al. Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription. eLife. 2014 Mar 25;3. e01632. https://doi.org/10.7554/eLife.01632