Antagonism between H3K27me3 and genome-lamina association drives atypical spatial genome organization in the totipotent embryo

Isabel Guerreiro; Franka J Rang; Yumiko K Kawamura; Carla Kroon-Veenboer; Jeroen Korving; Femke C Groenveld; Ramada E van Beek; Silke J A Lochs; Ellen Boele; Antoine H M F Peters; Jop Kind

doi:10.1038/s41588-024-01902-8

Antagonism between H3K27me3 and genome-lamina association drives atypical spatial genome organization in the totipotent embryo

Isabel Guerreiro, Franka J Rang, Yumiko K Kawamura, Carla Kroon-Veenboer, Jeroen Korving, Femke C Groenveld, Ramada E van Beek, Silke J A Lochs, Ellen Boele, Antoine H M F Peters, Jop Kind

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

1 Citation (Scopus)

Abstract

In mammals, early embryonic development exhibits highly unusual spatial positioning of genomic regions at the nuclear lamina, but the mechanisms underpinning this atypical genome organization remain elusive. Here, we generated single-cell profiles of lamina-associated domains (LADs) coupled with transcriptomics, which revealed a striking overlap between preimplantation-specific LAD dissociation and noncanonical broad domains of H3K27me3. Loss of H3K27me3 resulted in a restoration of canonical LAD profiles, suggesting an antagonistic relationship between lamina association and H3K27me3. Tethering of H3K27me3 to the nuclear periphery showed that the resultant relocalization is partially dependent on the underlying DNA sequence. Collectively, our results suggest that the atypical organization of LADs in early developmental stages is the result of a tug-of-war between intrinsic affinity for the nuclear lamina and H3K27me3, constrained by the available space at the nuclear periphery. This study provides detailed insight into the molecular mechanisms regulating nuclear organization during early mammalian development.

Original language	English
Pages (from-to)	2228-2237
Number of pages	10
Journal	Nature Genetics
Volume	56
Issue number	10
DOIs	https://doi.org/10.1038/s41588-024-01902-8
Publication status	Published - 2024

Keywords

Histones/metabolism
Animals
Mice
Genome/genetics
Nuclear Lamina/metabolism
Embryonic Development/genetics
Gene Expression Regulation, Developmental
Embryo, Mammalian/metabolism
Female
Single-Cell Analysis/methods

Access to Document

10.1038/s41588-024-01902-8

Cite this

Guerreiro, I., Rang, F. J., Kawamura, Y. K., Kroon-Veenboer, C., Korving, J., Groenveld, F. C., van Beek, R. E., Lochs, S. J. A., Boele, E., Peters, A. H. M. F., & Kind, J. (2024). Antagonism between H3K27me3 and genome-lamina association drives atypical spatial genome organization in the totipotent embryo. Nature Genetics, 56(10), 2228-2237. https://doi.org/10.1038/s41588-024-01902-8

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title = "Antagonism between H3K27me3 and genome-lamina association drives atypical spatial genome organization in the totipotent embryo",

abstract = "In mammals, early embryonic development exhibits highly unusual spatial positioning of genomic regions at the nuclear lamina, but the mechanisms underpinning this atypical genome organization remain elusive. Here, we generated single-cell profiles of lamina-associated domains (LADs) coupled with transcriptomics, which revealed a striking overlap between preimplantation-specific LAD dissociation and noncanonical broad domains of H3K27me3. Loss of H3K27me3 resulted in a restoration of canonical LAD profiles, suggesting an antagonistic relationship between lamina association and H3K27me3. Tethering of H3K27me3 to the nuclear periphery showed that the resultant relocalization is partially dependent on the underlying DNA sequence. Collectively, our results suggest that the atypical organization of LADs in early developmental stages is the result of a tug-of-war between intrinsic affinity for the nuclear lamina and H3K27me3, constrained by the available space at the nuclear periphery. This study provides detailed insight into the molecular mechanisms regulating nuclear organization during early mammalian development.",

keywords = "Histones/metabolism, Animals, Mice, Genome/genetics, Nuclear Lamina/metabolism, Embryonic Development/genetics, Gene Expression Regulation, Developmental, Embryo, Mammalian/metabolism, Female, Single-Cell Analysis/methods",

author = "Isabel Guerreiro and Rang, {Franka J} and Kawamura, {Yumiko K} and Carla Kroon-Veenboer and Jeroen Korving and Groenveld, {Femke C} and {van Beek}, {Ramada E} and Lochs, {Silke J A} and Ellen Boele and Peters, {Antoine H M F} and Jop Kind",

note = "{\textcopyright} 2024. The Author(s).",

year = "2024",

doi = "10.1038/s41588-024-01902-8",

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Guerreiro, I, Rang, FJ, Kawamura, YK, Kroon-Veenboer, C, Korving, J, Groenveld, FC, van Beek, RE, Lochs, SJA, Boele, E, Peters, AHMF & Kind, J 2024, 'Antagonism between H3K27me3 and genome-lamina association drives atypical spatial genome organization in the totipotent embryo', Nature Genetics, vol. 56, no. 10, pp. 2228-2237. https://doi.org/10.1038/s41588-024-01902-8

TY - JOUR

T1 - Antagonism between H3K27me3 and genome-lamina association drives atypical spatial genome organization in the totipotent embryo

AU - Guerreiro, Isabel

AU - Rang, Franka J

AU - Kawamura, Yumiko K

AU - Kroon-Veenboer, Carla

AU - Korving, Jeroen

AU - Groenveld, Femke C

AU - van Beek, Ramada E

AU - Lochs, Silke J A

AU - Boele, Ellen

AU - Peters, Antoine H M F

AU - Kind, Jop

PY - 2024

Y1 - 2024

N2 - In mammals, early embryonic development exhibits highly unusual spatial positioning of genomic regions at the nuclear lamina, but the mechanisms underpinning this atypical genome organization remain elusive. Here, we generated single-cell profiles of lamina-associated domains (LADs) coupled with transcriptomics, which revealed a striking overlap between preimplantation-specific LAD dissociation and noncanonical broad domains of H3K27me3. Loss of H3K27me3 resulted in a restoration of canonical LAD profiles, suggesting an antagonistic relationship between lamina association and H3K27me3. Tethering of H3K27me3 to the nuclear periphery showed that the resultant relocalization is partially dependent on the underlying DNA sequence. Collectively, our results suggest that the atypical organization of LADs in early developmental stages is the result of a tug-of-war between intrinsic affinity for the nuclear lamina and H3K27me3, constrained by the available space at the nuclear periphery. This study provides detailed insight into the molecular mechanisms regulating nuclear organization during early mammalian development.

AB - In mammals, early embryonic development exhibits highly unusual spatial positioning of genomic regions at the nuclear lamina, but the mechanisms underpinning this atypical genome organization remain elusive. Here, we generated single-cell profiles of lamina-associated domains (LADs) coupled with transcriptomics, which revealed a striking overlap between preimplantation-specific LAD dissociation and noncanonical broad domains of H3K27me3. Loss of H3K27me3 resulted in a restoration of canonical LAD profiles, suggesting an antagonistic relationship between lamina association and H3K27me3. Tethering of H3K27me3 to the nuclear periphery showed that the resultant relocalization is partially dependent on the underlying DNA sequence. Collectively, our results suggest that the atypical organization of LADs in early developmental stages is the result of a tug-of-war between intrinsic affinity for the nuclear lamina and H3K27me3, constrained by the available space at the nuclear periphery. This study provides detailed insight into the molecular mechanisms regulating nuclear organization during early mammalian development.

KW - Histones/metabolism

KW - Animals

KW - Mice

KW - Genome/genetics

KW - Nuclear Lamina/metabolism

KW - Embryonic Development/genetics

KW - Gene Expression Regulation, Developmental

KW - Embryo, Mammalian/metabolism

KW - Female

KW - Single-Cell Analysis/methods

U2 - 10.1038/s41588-024-01902-8

DO - 10.1038/s41588-024-01902-8

M3 - Article

C2 - 39284976

SN - 1061-4036

VL - 56

SP - 2228

EP - 2237

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -