Tags

Type your tag names separated by a space and hit enter

RBPJ, the major transcriptional effector of Notch signaling, remains associated with chromatin throughout mitosis, suggesting a role in mitotic bookmarking.
PLoS Genet. 2014 Mar; 10(3):e1004204.PG

Abstract

Mechanisms that maintain transcriptional memory through cell division are important to maintain cell identity, and sequence-specific transcription factors that remain associated with mitotic chromatin are emerging as key players in transcriptional memory propagation. Here, we show that the major transcriptional effector of Notch signaling, RBPJ, is retained on mitotic chromatin, and that this mitotic chromatin association is mediated through the direct association of RBPJ with DNA. We further demonstrate that RBPJ binds directly to nucleosomal DNA in vitro, with a preference for sites close to the entry/exit position of the nucleosomal DNA. Genome-wide analysis in the murine embryonal-carcinoma cell line F9 revealed that roughly 60% of the sites occupied by RBPJ in asynchronous cells were also occupied in mitotic cells. Among them, we found that a fraction of RBPJ occupancy sites shifted between interphase and mitosis, suggesting that RBPJ can be retained on mitotic chromatin by sliding on DNA rather than disengaging from chromatin during mitotic chromatin condensation. We propose that RBPJ can function as a mitotic bookmark, marking genes for efficient transcriptional activation or repression upon mitotic exit. Strikingly, we found that sites of RBPJ occupancy were enriched for CTCF-binding motifs in addition to RBPJ-binding motifs, and that RBPJ and CTCF interact. Given that CTCF regulates transcription and bridges long-range chromatin interactions, our results raise the intriguing hypothesis that by collaborating with CTCF, RBPJ may participate in establishing chromatin domains and/or long-range chromatin interactions that could be propagated through cell division to maintain gene expression programs.

Authors+Show Affiliations

Epigenetics Program, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.Epigenetics Program, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.Institute for Diabetes Obesity and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.Institute for Diabetes Obesity and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.Epigenetics Program, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Institute for Diabetes Obesity and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24603501

Citation

Lake, Robert J., et al. "RBPJ, the Major Transcriptional Effector of Notch Signaling, Remains Associated With Chromatin Throughout Mitosis, Suggesting a Role in Mitotic Bookmarking." PLoS Genetics, vol. 10, no. 3, 2014, pp. e1004204.
Lake RJ, Tsai PF, Choi I, et al. RBPJ, the major transcriptional effector of Notch signaling, remains associated with chromatin throughout mitosis, suggesting a role in mitotic bookmarking. PLoS Genet. 2014;10(3):e1004204.
Lake, R. J., Tsai, P. F., Choi, I., Won, K. J., & Fan, H. Y. (2014). RBPJ, the major transcriptional effector of Notch signaling, remains associated with chromatin throughout mitosis, suggesting a role in mitotic bookmarking. PLoS Genetics, 10(3), e1004204. https://doi.org/10.1371/journal.pgen.1004204
Lake RJ, et al. RBPJ, the Major Transcriptional Effector of Notch Signaling, Remains Associated With Chromatin Throughout Mitosis, Suggesting a Role in Mitotic Bookmarking. PLoS Genet. 2014;10(3):e1004204. PubMed PMID: 24603501.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - RBPJ, the major transcriptional effector of Notch signaling, remains associated with chromatin throughout mitosis, suggesting a role in mitotic bookmarking. AU - Lake,Robert J, AU - Tsai,Pei-Fang, AU - Choi,Inchan, AU - Won,Kyoung-Jae, AU - Fan,Hua-Ying, Y1 - 2014/03/06/ PY - 2013/04/12/received PY - 2014/01/13/accepted PY - 2014/3/8/entrez PY - 2014/3/8/pubmed PY - 2014/12/15/medline SP - e1004204 EP - e1004204 JF - PLoS genetics JO - PLoS Genet. VL - 10 IS - 3 N2 - Mechanisms that maintain transcriptional memory through cell division are important to maintain cell identity, and sequence-specific transcription factors that remain associated with mitotic chromatin are emerging as key players in transcriptional memory propagation. Here, we show that the major transcriptional effector of Notch signaling, RBPJ, is retained on mitotic chromatin, and that this mitotic chromatin association is mediated through the direct association of RBPJ with DNA. We further demonstrate that RBPJ binds directly to nucleosomal DNA in vitro, with a preference for sites close to the entry/exit position of the nucleosomal DNA. Genome-wide analysis in the murine embryonal-carcinoma cell line F9 revealed that roughly 60% of the sites occupied by RBPJ in asynchronous cells were also occupied in mitotic cells. Among them, we found that a fraction of RBPJ occupancy sites shifted between interphase and mitosis, suggesting that RBPJ can be retained on mitotic chromatin by sliding on DNA rather than disengaging from chromatin during mitotic chromatin condensation. We propose that RBPJ can function as a mitotic bookmark, marking genes for efficient transcriptional activation or repression upon mitotic exit. Strikingly, we found that sites of RBPJ occupancy were enriched for CTCF-binding motifs in addition to RBPJ-binding motifs, and that RBPJ and CTCF interact. Given that CTCF regulates transcription and bridges long-range chromatin interactions, our results raise the intriguing hypothesis that by collaborating with CTCF, RBPJ may participate in establishing chromatin domains and/or long-range chromatin interactions that could be propagated through cell division to maintain gene expression programs. SN - 1553-7404 UR - https://www.unboundmedicine.com/medline/citation/24603501/RBPJ_the_major_transcriptional_effector_of_Notch_signaling_remains_associated_with_chromatin_throughout_mitosis_suggesting_a_role_in_mitotic_bookmarking_ L2 - http://dx.plos.org/10.1371/journal.pgen.1004204 DB - PRIME DP - Unbound Medicine ER -