Publication

PRC1 Prevents Replication Stress during Chondrogenic Transit Amplification

Spaapen, F., Eijssen, L. M. T., Adriaens, M. E., Welting, T. J., Prickaerts, P., Salvaing, J., Dahlmans, V. E. H., Surtel, D. A. M., Kruitz, F., Kuijer, R., Takihara, Y., Marks, H., Stunnenberg, H. G., Wouters, B. G., Vidal, M. & Voncken, J. W., Dec-2017, In : Epigenomes. 1, 3, 31 p., 22.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Spaapen, F., Eijssen, L. M. T., Adriaens, M. E., Welting, T. J., Prickaerts, P., Salvaing, J., Dahlmans, V. E. H., Surtel, D. A. M., Kruitz, F., Kuijer, R., Takihara, Y., Marks, H., Stunnenberg, H. G., Wouters, B. G., Vidal, M., & Voncken, J. W. (2017). PRC1 Prevents Replication Stress during Chondrogenic Transit Amplification. Epigenomes, 1(3), [22]. https://doi.org/10.3390/epigenomes1030022

Author

Spaapen, Frank ; Eijssen, Lars M. T. ; Adriaens, Michiel E. ; Welting, Tim J. ; Prickaerts, Peggy ; Salvaing, Juliette ; Dahlmans, Vivian E. H. ; Surtel, Donald A. M. ; Kruitz, Frans ; Kuijer, Roel ; Takihara, Yoshihiro ; Marks, Hendrik ; Stunnenberg, Hendrik G. ; Wouters, Bradly G. ; Vidal, Miguel ; Voncken, Jan Willem. / PRC1 Prevents Replication Stress during Chondrogenic Transit Amplification. In: Epigenomes. 2017 ; Vol. 1, No. 3.

Harvard

Spaapen, F, Eijssen, LMT, Adriaens, ME, Welting, TJ, Prickaerts, P, Salvaing, J, Dahlmans, VEH, Surtel, DAM, Kruitz, F, Kuijer, R, Takihara, Y, Marks, H, Stunnenberg, HG, Wouters, BG, Vidal, M & Voncken, JW 2017, 'PRC1 Prevents Replication Stress during Chondrogenic Transit Amplification', Epigenomes, vol. 1, no. 3, 22. https://doi.org/10.3390/epigenomes1030022

Standard

PRC1 Prevents Replication Stress during Chondrogenic Transit Amplification. / Spaapen, Frank; Eijssen, Lars M. T.; Adriaens, Michiel E.; Welting, Tim J.; Prickaerts, Peggy; Salvaing, Juliette; Dahlmans, Vivian E. H.; Surtel, Donald A. M.; Kruitz, Frans; Kuijer, Roel; Takihara, Yoshihiro; Marks, Hendrik; Stunnenberg, Hendrik G.; Wouters, Bradly G.; Vidal, Miguel; Voncken, Jan Willem.

In: Epigenomes, Vol. 1, No. 3, 22, 12.2017.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Spaapen F, Eijssen LMT, Adriaens ME, Welting TJ, Prickaerts P, Salvaing J et al. PRC1 Prevents Replication Stress during Chondrogenic Transit Amplification. Epigenomes. 2017 Dec;1(3). 22. https://doi.org/10.3390/epigenomes1030022


BibTeX

@article{107237dfd7584c3bae7b9eba1129cd0e,
title = "PRC1 Prevents Replication Stress during Chondrogenic Transit Amplification",
abstract = "Transit amplification (TA), a state of combined, rapid proliferative expansion and differentiation of stem cell-descendants, remains poorly defined at the molecular level. The Polycomb Repressive Complex 1 (PRC1) protein BMI1 has been localized to TA compartments, yet its exact role in TA is unclear. PRC1 proteins control gene expression, cell proliferation and DNA-damage repair. Coordination of such DNA-templated activities during TA is predicted to be crucial to support DNA replication and differentiation-associated transcriptional programming. We here examined whether chondrogenesis provides a relevant biological context for synchronized coordination of these chromatin-based tasks by BMI1. Taking advantage of a prominently featuring TA-phase during chondrogenesis in vitro and in vivo, we here report that TA is completely dependent on intact PRC1 function. BMI1-depleted chondrogenic progenitors rapidly accumulate double strand DNA breaks during DNA replication, present massive non-H3K27me3-directed transcriptional deregulation and fail to undergo chondrogenic TA. Genome-wide accumulation of Topoisomerase 2 alpha and Geminin suggests a model in which PRC1 synchronizes replication and transcription during rapid chondrogenic progenitor expansion. Our combined data reveals for the first time a vital cell-autonomous role for PRC1 during chondrogenesis. We provide evidence that chondrocyte hyper-replication and hypertrophy represent a unique example of programmed senescence in vivo. These findings provide new perspectives on PRC1 function in development and disease.",
keywords = "polycomb, topoisomerase, transit amplification, chromatin, DNA replication, transcription, chondrogenesis, differentiation, DNA damage, hypertrophy, senescence",
author = "Frank Spaapen and Eijssen, {Lars M. T.} and Adriaens, {Michiel E.} and Welting, {Tim J.} and Peggy Prickaerts and Juliette Salvaing and Dahlmans, {Vivian E. H.} and Surtel, {Donald A. M.} and Frans Kruitz and Roel Kuijer and Yoshihiro Takihara and Hendrik Marks and Stunnenberg, {Hendrik G.} and Wouters, {Bradly G.} and Miguel Vidal and Voncken, {Jan Willem}",
year = "2017",
month = dec,
doi = "10.3390/epigenomes1030022",
language = "English",
volume = "1",
journal = "Epigenomes",
issn = "2075-4655",
publisher = "MDPI AG",
number = "3",

}

RIS

TY - JOUR

T1 - PRC1 Prevents Replication Stress during Chondrogenic Transit Amplification

AU - Spaapen, Frank

AU - Eijssen, Lars M. T.

AU - Adriaens, Michiel E.

AU - Welting, Tim J.

AU - Prickaerts, Peggy

AU - Salvaing, Juliette

AU - Dahlmans, Vivian E. H.

AU - Surtel, Donald A. M.

AU - Kruitz, Frans

AU - Kuijer, Roel

AU - Takihara, Yoshihiro

AU - Marks, Hendrik

AU - Stunnenberg, Hendrik G.

AU - Wouters, Bradly G.

AU - Vidal, Miguel

AU - Voncken, Jan Willem

PY - 2017/12

Y1 - 2017/12

N2 - Transit amplification (TA), a state of combined, rapid proliferative expansion and differentiation of stem cell-descendants, remains poorly defined at the molecular level. The Polycomb Repressive Complex 1 (PRC1) protein BMI1 has been localized to TA compartments, yet its exact role in TA is unclear. PRC1 proteins control gene expression, cell proliferation and DNA-damage repair. Coordination of such DNA-templated activities during TA is predicted to be crucial to support DNA replication and differentiation-associated transcriptional programming. We here examined whether chondrogenesis provides a relevant biological context for synchronized coordination of these chromatin-based tasks by BMI1. Taking advantage of a prominently featuring TA-phase during chondrogenesis in vitro and in vivo, we here report that TA is completely dependent on intact PRC1 function. BMI1-depleted chondrogenic progenitors rapidly accumulate double strand DNA breaks during DNA replication, present massive non-H3K27me3-directed transcriptional deregulation and fail to undergo chondrogenic TA. Genome-wide accumulation of Topoisomerase 2 alpha and Geminin suggests a model in which PRC1 synchronizes replication and transcription during rapid chondrogenic progenitor expansion. Our combined data reveals for the first time a vital cell-autonomous role for PRC1 during chondrogenesis. We provide evidence that chondrocyte hyper-replication and hypertrophy represent a unique example of programmed senescence in vivo. These findings provide new perspectives on PRC1 function in development and disease.

AB - Transit amplification (TA), a state of combined, rapid proliferative expansion and differentiation of stem cell-descendants, remains poorly defined at the molecular level. The Polycomb Repressive Complex 1 (PRC1) protein BMI1 has been localized to TA compartments, yet its exact role in TA is unclear. PRC1 proteins control gene expression, cell proliferation and DNA-damage repair. Coordination of such DNA-templated activities during TA is predicted to be crucial to support DNA replication and differentiation-associated transcriptional programming. We here examined whether chondrogenesis provides a relevant biological context for synchronized coordination of these chromatin-based tasks by BMI1. Taking advantage of a prominently featuring TA-phase during chondrogenesis in vitro and in vivo, we here report that TA is completely dependent on intact PRC1 function. BMI1-depleted chondrogenic progenitors rapidly accumulate double strand DNA breaks during DNA replication, present massive non-H3K27me3-directed transcriptional deregulation and fail to undergo chondrogenic TA. Genome-wide accumulation of Topoisomerase 2 alpha and Geminin suggests a model in which PRC1 synchronizes replication and transcription during rapid chondrogenic progenitor expansion. Our combined data reveals for the first time a vital cell-autonomous role for PRC1 during chondrogenesis. We provide evidence that chondrocyte hyper-replication and hypertrophy represent a unique example of programmed senescence in vivo. These findings provide new perspectives on PRC1 function in development and disease.

KW - polycomb

KW - topoisomerase

KW - transit amplification

KW - chromatin

KW - DNA replication

KW - transcription

KW - chondrogenesis

KW - differentiation

KW - DNA damage

KW - hypertrophy

KW - senescence

U2 - 10.3390/epigenomes1030022

DO - 10.3390/epigenomes1030022

M3 - Article

VL - 1

JO - Epigenomes

JF - Epigenomes

SN - 2075-4655

IS - 3

M1 - 22

ER -

ID: 100481349