Chromosomal coordination and differential structure of asynchronous replicating regions

Britny Blumenfeld; Hagit Masika; Marganit Farago; Yishai Yehuda; Lamia Halaseh; Oriya Vardi; Rachel Rapoport; Rena Levin-Klein; Howard Cedar; Yehudit Bergman; Itamar Simon

doi:10.1038/s41467-021-21348-4

Chromosomal coordination and differential structure of asynchronous replicating regions

Britny Blumenfeld, Hagit Masika, Marganit Farago, Yishai Yehuda, Lamia Halaseh, Oriya Vardi, Rachel Rapoport, Rena Levin-Klein, Howard Cedar, Yehudit Bergman, Itamar Simon^*

^*Corresponding author for this work

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

6 Scopus citations

Abstract

Stochastic asynchronous replication timing (AS-RT) is a phenomenon in which the time of replication of each allele is different, and the identity of the early allele varies between cells. By taking advantage of stable clonal pre-B cell populations derived from C57BL6/Castaneous mice, we have mapped the genome-wide AS-RT loci, independently of genetic differences. These regions are characterized by differential chromatin accessibility, mono-allelic expression and include new gene families involved in specifying cell identity. By combining population level mapping with single cell FISH, our data reveal the existence of a novel regulatory program that coordinates a fixed relationship between AS-RT regions on any given chromosome, with some loci set to replicate in a parallel and others set in the anti-parallel orientation. Our results show that AS-RT is a highly regulated epigenetic mark established during early embryogenesis that may be used for facilitating the programming of mono-allelic choice throughout development.

Original language	American English
Article number	1035
Pages (from-to)	1-12
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-21348-4
State	Published - 1 Dec 2021

Bibliographical note

Funding Information:
We thank the members of the Core Research Facility in the Hebrew University School of Medicine; Dr. Dan Lehmann and Dr. Eleonora Medvedev for assistance with the FACS analysis; Dr. Idit Shiff, Dr. Abed Nasereddin and Ms. Alexia Azoulay for generating genomic data. This work was supported by research grants from the Israel Academy of Sciences (grant # 734/13 and #1228/18 to Y.B., grant #282/16 to H.C., grant # 184/16 to I.S.), ISF-NSFC (grant #2013/14 to Y.B., grant #2555/16 to I.S.), the Israel Cancer Research Foundation (I.S. and grant # 211410 to Y.B., grant #210910 to H.C.,), The Binational Science Foundation (grant # 2100289 to Y.B.), the Emanuel Rubin Chair in Medical Sciences (Y.B.), the Israel Center of Excellence Program (grant #1796/12 to Y.B.), the German Israeli Foundation (grant # 1424 to Y.B.), Rosetrees Foundation (H.C.).

Publisher Copyright:
© 2021, The Author(s).

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title = "Chromosomal coordination and differential structure of asynchronous replicating regions",

abstract = "Stochastic asynchronous replication timing (AS-RT) is a phenomenon in which the time of replication of each allele is different, and the identity of the early allele varies between cells. By taking advantage of stable clonal pre-B cell populations derived from C57BL6/Castaneous mice, we have mapped the genome-wide AS-RT loci, independently of genetic differences. These regions are characterized by differential chromatin accessibility, mono-allelic expression and include new gene families involved in specifying cell identity. By combining population level mapping with single cell FISH, our data reveal the existence of a novel regulatory program that coordinates a fixed relationship between AS-RT regions on any given chromosome, with some loci set to replicate in a parallel and others set in the anti-parallel orientation. Our results show that AS-RT is a highly regulated epigenetic mark established during early embryogenesis that may be used for facilitating the programming of mono-allelic choice throughout development.",

author = "Britny Blumenfeld and Hagit Masika and Marganit Farago and Yishai Yehuda and Lamia Halaseh and Oriya Vardi and Rachel Rapoport and Rena Levin-Klein and Howard Cedar and Yehudit Bergman and Itamar Simon",

note = "Funding Information: We thank the members of the Core Research Facility in the Hebrew University School of Medicine; Dr. Dan Lehmann and Dr. Eleonora Medvedev for assistance with the FACS analysis; Dr. Idit Shiff, Dr. Abed Nasereddin and Ms. Alexia Azoulay for generating genomic data. This work was supported by research grants from the Israel Academy of Sciences (grant # 734/13 and #1228/18 to Y.B., grant #282/16 to H.C., grant # 184/16 to I.S.), ISF-NSFC (grant #2013/14 to Y.B., grant #2555/16 to I.S.), the Israel Cancer Research Foundation (I.S. and grant # 211410 to Y.B., grant #210910 to H.C.,), The Binational Science Foundation (grant # 2100289 to Y.B.), the Emanuel Rubin Chair in Medical Sciences (Y.B.), the Israel Center of Excellence Program (grant #1796/12 to Y.B.), the German Israeli Foundation (grant # 1424 to Y.B.), Rosetrees Foundation (H.C.). Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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AU - Masika, Hagit

AU - Farago, Marganit

AU - Yehuda, Yishai

AU - Halaseh, Lamia

AU - Vardi, Oriya

AU - Rapoport, Rachel

AU - Levin-Klein, Rena

AU - Cedar, Howard

AU - Bergman, Yehudit

AU - Simon, Itamar

N1 - Funding Information: We thank the members of the Core Research Facility in the Hebrew University School of Medicine; Dr. Dan Lehmann and Dr. Eleonora Medvedev for assistance with the FACS analysis; Dr. Idit Shiff, Dr. Abed Nasereddin and Ms. Alexia Azoulay for generating genomic data. This work was supported by research grants from the Israel Academy of Sciences (grant # 734/13 and #1228/18 to Y.B., grant #282/16 to H.C., grant # 184/16 to I.S.), ISF-NSFC (grant #2013/14 to Y.B., grant #2555/16 to I.S.), the Israel Cancer Research Foundation (I.S. and grant # 211410 to Y.B., grant #210910 to H.C.,), The Binational Science Foundation (grant # 2100289 to Y.B.), the Emanuel Rubin Chair in Medical Sciences (Y.B.), the Israel Center of Excellence Program (grant #1796/12 to Y.B.), the German Israeli Foundation (grant # 1424 to Y.B.), Rosetrees Foundation (H.C.). Publisher Copyright: © 2021, The Author(s).

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N2 - Stochastic asynchronous replication timing (AS-RT) is a phenomenon in which the time of replication of each allele is different, and the identity of the early allele varies between cells. By taking advantage of stable clonal pre-B cell populations derived from C57BL6/Castaneous mice, we have mapped the genome-wide AS-RT loci, independently of genetic differences. These regions are characterized by differential chromatin accessibility, mono-allelic expression and include new gene families involved in specifying cell identity. By combining population level mapping with single cell FISH, our data reveal the existence of a novel regulatory program that coordinates a fixed relationship between AS-RT regions on any given chromosome, with some loci set to replicate in a parallel and others set in the anti-parallel orientation. Our results show that AS-RT is a highly regulated epigenetic mark established during early embryogenesis that may be used for facilitating the programming of mono-allelic choice throughout development.

AB - Stochastic asynchronous replication timing (AS-RT) is a phenomenon in which the time of replication of each allele is different, and the identity of the early allele varies between cells. By taking advantage of stable clonal pre-B cell populations derived from C57BL6/Castaneous mice, we have mapped the genome-wide AS-RT loci, independently of genetic differences. These regions are characterized by differential chromatin accessibility, mono-allelic expression and include new gene families involved in specifying cell identity. By combining population level mapping with single cell FISH, our data reveal the existence of a novel regulatory program that coordinates a fixed relationship between AS-RT regions on any given chromosome, with some loci set to replicate in a parallel and others set in the anti-parallel orientation. Our results show that AS-RT is a highly regulated epigenetic mark established during early embryogenesis that may be used for facilitating the programming of mono-allelic choice throughout development.

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Chromosomal coordination and differential structure of asynchronous replicating regions

Abstract

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