ATXN3 controls DNA replication and transcription by regulating chromatin structure

Research output: Contribution to journal › Journal article › Research › peer-review

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ATXN3 controls DNA replication and transcription by regulating chromatin structure. / Hernández-Carralero, Esperanza; Cabrera, Elisa; Rodríguez-Torres, Gara; Hernández-Reyes, Yeray; Singh, Abhay N; Santa-María, Cristina; Fernández-Justel, José Miguel; Janssens, Roel C; Marteijn, Jurgen A; Evert, Bernd O; Mailand, Niels; Gómez, María; Ramadan, Kristijan; Smits, Veronique A J; Freire, Raimundo.

In: Nucleic Acids Research, Vol. 51, No. 11, 2023, p. 5396–5413.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hernández-Carralero, E, Cabrera, E, Rodríguez-Torres, G, Hernández-Reyes, Y, Singh, AN, Santa-María, C, Fernández-Justel, JM, Janssens, RC, Marteijn, JA, Evert, BO, Mailand, N, Gómez, M, Ramadan, K, Smits, VAJ & Freire, R 2023, 'ATXN3 controls DNA replication and transcription by regulating chromatin structure', Nucleic Acids Research, vol. 51, no. 11, pp. 5396–5413. https://doi.org/10.1093/nar/gkad212

APA

Hernández-Carralero, E., Cabrera, E., Rodríguez-Torres, G., Hernández-Reyes, Y., Singh, A. N., Santa-María, C., Fernández-Justel, J. M., Janssens, R. C., Marteijn, J. A., Evert, B. O., Mailand, N., Gómez, M., Ramadan, K., Smits, V. A. J., & Freire, R. (2023). ATXN3 controls DNA replication and transcription by regulating chromatin structure. Nucleic Acids Research, 51(11), 5396–5413. https://doi.org/10.1093/nar/gkad212

Vancouver

Hernández-Carralero E, Cabrera E, Rodríguez-Torres G, Hernández-Reyes Y, Singh AN, Santa-María C et al. ATXN3 controls DNA replication and transcription by regulating chromatin structure. Nucleic Acids Research. 2023;51(11):5396–5413. https://doi.org/10.1093/nar/gkad212

Author

Hernández-Carralero, Esperanza ; Cabrera, Elisa ; Rodríguez-Torres, Gara ; Hernández-Reyes, Yeray ; Singh, Abhay N ; Santa-María, Cristina ; Fernández-Justel, José Miguel ; Janssens, Roel C ; Marteijn, Jurgen A ; Evert, Bernd O ; Mailand, Niels ; Gómez, María ; Ramadan, Kristijan ; Smits, Veronique A J ; Freire, Raimundo. / ATXN3 controls DNA replication and transcription by regulating chromatin structure. In: Nucleic Acids Research. 2023 ; Vol. 51, No. 11. pp. 5396–5413.

Bibtex

@article{6e807394b95b4288a7ff5dcad3fd210f,
title = "ATXN3 controls DNA replication and transcription by regulating chromatin structure",
abstract = "The deubiquitinating enzyme Ataxin-3 (ATXN3) contains a polyglutamine (PolyQ) region, the expansion of which causes spinocerebellar ataxia type-3 (SCA3). ATXN3 has multiple functions, such as regulating transcription or controlling genomic stability after DNA damage. Here we report the role of ATXN3 in chromatin organization during unperturbed conditions, in a catalytic-independent manner. The lack of ATXN3 leads to abnormalities in nuclear and nucleolar morphology, alters DNA replication timing and increases transcription. Additionally, indicators of more open chromatin, such as increased mobility of histone H1, changes in epigenetic marks and higher sensitivity to micrococcal nuclease digestion were detected in the absence of ATXN3. Interestingly, the effects observed in cells lacking ATXN3 are epistatic to the inhibition or lack of the histone deacetylase 3 (HDAC3), an interaction partner of ATXN3. The absence of ATXN3 decreases the recruitment of endogenous HDAC3 to the chromatin, as well as the HDAC3 nuclear/cytoplasm ratio after HDAC3 overexpression, suggesting that ATXN3 controls the subcellular localization of HDAC3. Importantly, the overexpression of a PolyQ-expanded version of ATXN3 behaves as a null mutant, altering DNA replication parameters, epigenetic marks and the subcellular distribution of HDAC3, giving new insights into the molecular basis of the disease.",
author = "Esperanza Hern{\'a}ndez-Carralero and Elisa Cabrera and Gara Rodr{\'i}guez-Torres and Yeray Hern{\'a}ndez-Reyes and Singh, {Abhay N} and Cristina Santa-Mar{\'i}a and Fern{\'a}ndez-Justel, {Jos{\'e} Miguel} and Janssens, {Roel C} and Marteijn, {Jurgen A} and Evert, {Bernd O} and Niels Mailand and Mar{\'i}a G{\'o}mez and Kristijan Ramadan and Smits, {Veronique A J} and Raimundo Freire",
note = "{\textcopyright} The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.",
year = "2023",
doi = "10.1093/nar/gkad212",
language = "English",
volume = "51",
pages = "5396–5413",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "11",

}

RIS

TY - JOUR

T1 - ATXN3 controls DNA replication and transcription by regulating chromatin structure

AU - Hernández-Carralero, Esperanza

AU - Cabrera, Elisa

AU - Rodríguez-Torres, Gara

AU - Hernández-Reyes, Yeray

AU - Singh, Abhay N

AU - Santa-María, Cristina

AU - Fernández-Justel, José Miguel

AU - Janssens, Roel C

AU - Marteijn, Jurgen A

AU - Evert, Bernd O

AU - Mailand, Niels

AU - Gómez, María

AU - Ramadan, Kristijan

AU - Smits, Veronique A J

AU - Freire, Raimundo

N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2023

Y1 - 2023

N2 - The deubiquitinating enzyme Ataxin-3 (ATXN3) contains a polyglutamine (PolyQ) region, the expansion of which causes spinocerebellar ataxia type-3 (SCA3). ATXN3 has multiple functions, such as regulating transcription or controlling genomic stability after DNA damage. Here we report the role of ATXN3 in chromatin organization during unperturbed conditions, in a catalytic-independent manner. The lack of ATXN3 leads to abnormalities in nuclear and nucleolar morphology, alters DNA replication timing and increases transcription. Additionally, indicators of more open chromatin, such as increased mobility of histone H1, changes in epigenetic marks and higher sensitivity to micrococcal nuclease digestion were detected in the absence of ATXN3. Interestingly, the effects observed in cells lacking ATXN3 are epistatic to the inhibition or lack of the histone deacetylase 3 (HDAC3), an interaction partner of ATXN3. The absence of ATXN3 decreases the recruitment of endogenous HDAC3 to the chromatin, as well as the HDAC3 nuclear/cytoplasm ratio after HDAC3 overexpression, suggesting that ATXN3 controls the subcellular localization of HDAC3. Importantly, the overexpression of a PolyQ-expanded version of ATXN3 behaves as a null mutant, altering DNA replication parameters, epigenetic marks and the subcellular distribution of HDAC3, giving new insights into the molecular basis of the disease.

AB - The deubiquitinating enzyme Ataxin-3 (ATXN3) contains a polyglutamine (PolyQ) region, the expansion of which causes spinocerebellar ataxia type-3 (SCA3). ATXN3 has multiple functions, such as regulating transcription or controlling genomic stability after DNA damage. Here we report the role of ATXN3 in chromatin organization during unperturbed conditions, in a catalytic-independent manner. The lack of ATXN3 leads to abnormalities in nuclear and nucleolar morphology, alters DNA replication timing and increases transcription. Additionally, indicators of more open chromatin, such as increased mobility of histone H1, changes in epigenetic marks and higher sensitivity to micrococcal nuclease digestion were detected in the absence of ATXN3. Interestingly, the effects observed in cells lacking ATXN3 are epistatic to the inhibition or lack of the histone deacetylase 3 (HDAC3), an interaction partner of ATXN3. The absence of ATXN3 decreases the recruitment of endogenous HDAC3 to the chromatin, as well as the HDAC3 nuclear/cytoplasm ratio after HDAC3 overexpression, suggesting that ATXN3 controls the subcellular localization of HDAC3. Importantly, the overexpression of a PolyQ-expanded version of ATXN3 behaves as a null mutant, altering DNA replication parameters, epigenetic marks and the subcellular distribution of HDAC3, giving new insights into the molecular basis of the disease.

U2 - 10.1093/nar/gkad212

DO - 10.1093/nar/gkad212

M3 - Journal article

C2 - 36971114

VL - 51

SP - 5396

EP - 5413

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 11

ER -

ID: 342672969