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Article ; Online: Instruction of epigenetic states from DNA sequences.

Stelzer, Yonatan

2023 Volume 24, Issue 3, Page(s) 164

MeSH term(s)	Base Sequence ; Epigenesis, Genetic ; DNA Methylation
Language	English
Publishing date	2023-01-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2031313-5
ISSN	1471-0080 ; 1471-0072
ISSN (online)	1471-0080
ISSN	1471-0072
DOI	10.1038/s41580-023-00577-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 5446: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 26: Show issues

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Article ; Online: Induced epigenetic changes memorized across generations in mice.

Cheng, Saifeng / Mayshar, Yoav / Stelzer, Yonatan

Cell

2023 Volume 186, Issue 4, Page(s) 683–685

Abstract: Transgenerational epigenetic inheritance in mammals has long been debatable. In this issue of Cell, Takahashi et al. induce DNA methylation at promoter-associated CpG islands (CGIs) of two metabolism-related genes and show that the acquired epigenetic ... ...

Abstract	Transgenerational epigenetic inheritance in mammals has long been debatable. In this issue of Cell, Takahashi et al. induce DNA methylation at promoter-associated CpG islands (CGIs) of two metabolism-related genes and show that the acquired epigenetic changes and associated metabolic phenotypes are stably propagated across several generations in transgenic mice.
MeSH term(s)	Mice ; Animals ; Epigenesis, Genetic ; DNA Methylation ; Mammals/genetics ; Inheritance Patterns ; CpG Islands/genetics
Language	English
Publishing date	2023-02-20
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2023.01.023
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Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 58: Show issues

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Article ; Online: Balanced gene dosage control rather than parental origin underpins genomic imprinting.

Weinberg-Shukron, Ariella / Ben-Yair, Raz / Takahashi, Nozomi / Dunjić, Marko / Shtrikman, Alon / Edwards, Carol A / Ferguson-Smith, Anne C / Stelzer, Yonatan

Nature communications

2022 Volume 13, Issue 1, Page(s) 4391

Abstract: Mammalian parental imprinting represents an exquisite form of epigenetic control regulating the parent-specific monoallelic expression of genes in clusters. While imprinting perturbations are widely associated with developmental abnormalities, the ... ...

Abstract	Mammalian parental imprinting represents an exquisite form of epigenetic control regulating the parent-specific monoallelic expression of genes in clusters. While imprinting perturbations are widely associated with developmental abnormalities, the intricate regional interplay between imprinted genes makes interpreting the contribution of gene dosage effects to phenotypes a challenging task. Using mouse models with distinct deletions in an intergenic region controlling imprinting across the Dlk1-Dio3 domain, we link changes in genetic and epigenetic states to allelic-expression and phenotypic outcome in vivo. This determined how hierarchical interactions between regulatory elements orchestrate robust parent-specific expression, with implications for non-imprinted gene regulation. Strikingly, flipping imprinting on the parental chromosomes by crossing genotypes of complete and partial intergenic element deletions rescues the lethality of each deletion on its own. Our work indicates that parental origin of an epigenetic state is irrelevant as long as appropriate balanced gene expression is established and maintained at imprinted loci.
MeSH term(s)	Alleles ; Animals ; Chromosomes ; DNA Methylation/genetics ; DNA, Intergenic ; Gene Dosage ; Genomic Imprinting/genetics ; Mammals/genetics ; Mice
Chemical Substances	DNA, Intergenic
Language	English
Publishing date	2022-07-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-32144-z
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Article ; Online: Mouse embryo model derived exclusively from embryonic stem cells undergoes neurulation and heart development.

Lau, Kasey Y C / Rubinstein, Hernan / Gantner, Carlos W / Hadas, Ron / Amadei, Gianluca / Stelzer, Yonatan / Zernicka-Goetz, Magdalena

Cell stem cell

2022 Volume 29, Issue 10, Page(s) 1445–1458.e8

Abstract: Several in vitro models have been developed to recapitulate mouse embryogenesis solely from embryonic stem cells (ESCs). Despite mimicking many aspects of early development, they fail to capture the interactions between embryonic and extraembryonic ... ...

Abstract	Several in vitro models have been developed to recapitulate mouse embryogenesis solely from embryonic stem cells (ESCs). Despite mimicking many aspects of early development, they fail to capture the interactions between embryonic and extraembryonic tissues. To overcome this difficulty, we have developed a mouse ESC-based in vitro model that reconstitutes the pluripotent ESC lineage and the two extraembryonic lineages of the post-implantation embryo by transcription-factor-mediated induction. This unified model recapitulates developmental events from embryonic day 5.5 to 8.5, including gastrulation; formation of the anterior-posterior axis, brain, and a beating heart structure; and the development of extraembryonic tissues, including yolk sac and chorion. Comparing single-cell RNA sequencing from individual structures with time-matched natural embryos identified remarkably similar transcriptional programs across lineages but also showed when and where the model diverges from the natural program. Our findings demonstrate an extraordinary plasticity of ESCs to self-organize and generate a whole-embryo-like structure.
MeSH term(s)	Animals ; Embryo, Mammalian ; Embryonic Development ; Embryonic Stem Cells ; Mice ; Mouse Embryonic Stem Cells ; Neurulation
Language	English
Publishing date	2022-09-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2022.08.013
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Zs.A 6589: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 75: Show issues

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Article ; Online: Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells.

Dunjić, Marko / Jonas, Felix / Yaakov, Gilad / More, Roye / Mayshar, Yoav / Rais, Yoach / Orenbuch, Ayelet-Hashahar / Cheng, Saifeng / Barkai, Naama / Stelzer, Yonatan

Nature communications

2023 Volume 14, Issue 1, Page(s) 3791

Abstract: Eviction of histones from nucleosomes and their exchange with newly synthesized or alternative variants is a central epigenetic determinant. Here, we define the genome-wide occupancy and exchange pattern of canonical and non-canonical histone variants in ...

Abstract	Eviction of histones from nucleosomes and their exchange with newly synthesized or alternative variants is a central epigenetic determinant. Here, we define the genome-wide occupancy and exchange pattern of canonical and non-canonical histone variants in mouse embryonic stem cells by genetically encoded exchange sensors. While exchange of all measured variants scales with transcription, we describe variant-specific associations with transcription elongation and Polycomb binding. We found considerable exchange of H3.1 and H2B variants in heterochromatin and repeat elements, contrasting the occupancy and little exchange of H3.3 in these regions. This unexpected association between H3.3 occupancy and exchange of canonical variants is also evident in active promoters and enhancers, and further validated by reduced H3.1 dynamics following depletion of H3.3-specific chaperone, HIRA. Finally, analyzing transgenic mice harboring H3.1 or H3.3 sensors demonstrates the vast potential of this system for studying histone exchange and its impact on gene expression regulation in vivo.
MeSH term(s)	Animals ; Mice ; Histones/genetics ; Histones/metabolism ; Mouse Embryonic Stem Cells/metabolism ; Nucleosomes/genetics ; Regulatory Sequences, Nucleic Acid ; Gene Expression Regulation
Chemical Substances	Histones ; Nucleosomes
Language	English
Publishing date	2023-06-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-39477-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Time-aligned hourglass gastrulation models in rabbit and mouse.

Mayshar, Yoav / Raz, Ofir / Cheng, Saifeng / Ben-Yair, Raz / Hadas, Ron / Reines, Netta / Mittnenzweig, Markus / Ben-Kiki, Oren / Lifshitz, Aviezer / Tanay, Amos / Stelzer, Yonatan

Cell

2023 Volume 186, Issue 12, Page(s) 2610–2627.e18

Abstract: The hourglass model describes the convergence of species within the same phylum to a similar body plan during development; however, the molecular mechanisms underlying this phenomenon in mammals remain poorly described. Here, we compare rabbit and mouse ... ...

Abstract	The hourglass model describes the convergence of species within the same phylum to a similar body plan during development; however, the molecular mechanisms underlying this phenomenon in mammals remain poorly described. Here, we compare rabbit and mouse time-resolved differentiation trajectories to revisit this model at single-cell resolution. We modeled gastrulation dynamics using hundreds of embryos sampled between gestation days 6.0 and 8.5 and compared the species using a framework for time-resolved single-cell differentiation-flows analysis. We find convergence toward similar cell-state compositions at E7.5, supported by the quantitatively conserved expression of 76 transcription factors, despite divergence in surrounding trophoblast and hypoblast signaling. However, we observed noticeable changes in specification timing of some lineages and divergence of primordial germ cell programs, which in the rabbit do not activate mesoderm genes. Comparative analysis of temporal differentiation models provides a basis for studying the evolution of gastrulation dynamics across mammals.
MeSH term(s)	Animals ; Rabbits ; Mice ; Gastrulation/genetics ; Mesoderm/physiology ; Cell Differentiation/physiology ; Mammals/genetics ; Trophoblasts ; Gene Expression Regulation, Developmental
Language	English
Publishing date	2023-05-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2023.04.037
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Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 58: Show issues

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Article ; Online: Monitoring Dynamics of DNA Methylation at Single-Cell Resolution during Development and Disease.

Stelzer, Yonatan / Jaenisch, Rudolf

Cold Spring Harbor symposia on quantitative biology

2015 Volume 80, Page(s) 199–206

Abstract: DNA methylation is a broadly studied epigenetic modification that is essential for normal mammalian development. Over the years, numerous methodologies were developed trying to cope with the intrinsic challenge of reading the "second dimension" ... ...

Abstract	DNA methylation is a broadly studied epigenetic modification that is essential for normal mammalian development. Over the years, numerous methodologies were developed trying to cope with the intrinsic challenge of reading the "second dimension" epigenetic code. The recent rapid expansion of sequencing technologies has made it possible to fully chart the methylation landscape of different cell types at single-base resolution. Surprisingly, accumulating data suggest that, in addition to the massive epigenome remodeling during early development, cell type and tissue specification is associated with high levels of DNA methylation dynamics at distal regulatory elements. However, current methods provide only a static "snapshot" of DNA methylation, thus precluding the study of real-time methylation dynamics during cell fate changes. Here we review the principles of a new approach that enables monitoring loci-specific DNA methylation dynamics at single-cell resolution. We also discuss potential applications and promises for implementing this methodology to study DNA methylation changes during development and disease.
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1943-4456 ; 0091-7451
ISSN (online)	1943-4456
ISSN	0091-7451
DOI	10.1101/sqb.2015.80.027334
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Article ; Online: Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells

Marko Dunjić / Felix Jonas / Gilad Yaakov / Roye More / Yoav Mayshar / Yoach Rais / Ayelet-Hashahar Orenbuch / Saifeng Cheng / Naama Barkai / Yonatan Stelzer

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 19

Abstract: Abstract Eviction of histones from nucleosomes and their exchange with newly synthesized or alternative variants is a central epigenetic determinant. Here, we define the genome-wide occupancy and exchange pattern of canonical and non-canonical histone ... ...

Abstract	Abstract Eviction of histones from nucleosomes and their exchange with newly synthesized or alternative variants is a central epigenetic determinant. Here, we define the genome-wide occupancy and exchange pattern of canonical and non-canonical histone variants in mouse embryonic stem cells by genetically encoded exchange sensors. While exchange of all measured variants scales with transcription, we describe variant-specific associations with transcription elongation and Polycomb binding. We found considerable exchange of H3.1 and H2B variants in heterochromatin and repeat elements, contrasting the occupancy and little exchange of H3.3 in these regions. This unexpected association between H3.3 occupancy and exchange of canonical variants is also evident in active promoters and enhancers, and further validated by reduced H3.1 dynamics following depletion of H3.3-specific chaperone, HIRA. Finally, analyzing transgenic mice harboring H3.1 or H3.3 sensors demonstrates the vast potential of this system for studying histone exchange and its impact on gene expression regulation in vivo.
Keywords	Science ; Q
Subject code	572
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Deciphering the principles of the RNA editing code via large-scale systematic probing.

Uzonyi, Anna / Nir, Ronit / Shliefer, Ofir / Stern-Ginossar, Noam / Antebi, Yaron / Stelzer, Yonatan / Levanon, Erez Y / Schwartz, Schraga

Molecular cell

2021 Volume 81, Issue 11, Page(s) 2374–2387.e3

Abstract: Adenosine-to-inosine editing is catalyzed by ADAR1 at thousands of sites transcriptome-wide. Despite intense interest in ADAR1 from physiological, bioengineering, and therapeutic perspectives, the rules of ADAR1 substrate selection are poorly understood. ...

Abstract	Adenosine-to-inosine editing is catalyzed by ADAR1 at thousands of sites transcriptome-wide. Despite intense interest in ADAR1 from physiological, bioengineering, and therapeutic perspectives, the rules of ADAR1 substrate selection are poorly understood. Here, we used large-scale systematic probing of ∼2,000 synthetic constructs to explore the structure and sequence context determining editability. We uncover two structural layers determining the formation and propagation of A-to-I editing, independent of sequence. First, editing is robustly induced at fixed intervals of 35 bp upstream and 30 bp downstream of structural disruptions. Second, editing is symmetrically introduced on opposite sites on a double-stranded structure. Our findings suggest a recursive model for RNA editing, whereby the structural alteration induced by the editing at one site iteratively gives rise to the formation of an additional editing site at a fixed periodicity, serving as a basis for the propagation of editing along and across both strands of double-stranded RNA structures.
MeSH term(s)	A549 Cells ; Adenosine/genetics ; Adenosine/metabolism ; Adenosine Deaminase/genetics ; Adenosine Deaminase/metabolism ; Animals ; Base Pairing ; HEK293 Cells ; Humans ; Inosine/genetics ; Inosine/metabolism ; MCF-7 Cells ; Mice ; NIH 3T3 Cells ; Nucleic Acid Conformation ; RNA Editing ; RNA, Double-Stranded/chemistry ; RNA, Double-Stranded/genetics ; RNA, Double-Stranded/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism
Chemical Substances	RNA, Double-Stranded ; RNA-Binding Proteins ; Inosine (5A614L51CT) ; ADAR protein, human (EC 3.5.4.37) ; Adenosine Deaminase (EC 3.5.4.4) ; Adenosine (K72T3FS567)
Language	English
Publishing date	2021-04-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2021.03.024
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Article ; Online: Balanced gene dosage control rather than parental origin underpins genomic imprinting

Ariella Weinberg-Shukron / Raz Ben-Yair / Nozomi Takahashi / Marko Dunjić / Alon Shtrikman / Carol A. Edwards / Anne C. Ferguson-Smith / Yonatan Stelzer

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 12

Abstract: Here the authors investigate whether for imprinted genes the parent-of-origin of the expressed allele or rather appropriate gene dosage is more important for normal development. Using the differentially methylated region of Dlk1-Dio3 gene involved in ... ...

Abstract	Here the authors investigate whether for imprinted genes the parent-of-origin of the expressed allele or rather appropriate gene dosage is more important for normal development. Using the differentially methylated region of Dlk1-Dio3 gene involved in imprinting, they show that correct parent-of-origin imprinting pattern is secondary to balanced gene dosage.
Keywords	Science ; Q
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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