Jop Kind

Oncode Institute

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Co-Authors

Bas van Steensel

Oncode Institute

Kim L. de Luca

University Medical Center Utrecht

Isabel Guerreiro

University Medical Center Utrecht

Sandra S. de Vries

University Medical Center Utrecht

Silke J. A. Lochs

Oncode Institute

Franka J. Rang

Royal Netherlands Academy of Arts and Sciences

Asifa Akhtar

Max Planck Institute of Immunobiology and Epigenetics

Siddharth S. Dey

University of California, Santa Barbara

Koos Rooijers

Oncode Institute

Ludo Pagie

Oncode Institute

Cooperative Institutions

Oncode Institute

University Medical Center Utrecht

The Netherlands Cancer Institute

Royal Netherlands Academy of Arts and Sciences

Inserm

Centre National de la Recherche Scientifique

Max Planck Society

University of Geneva

Utrecht University

Hubrecht Institute for Developmental Biology and Stem Cell Research

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Cotranscriptional recruitment of the dosage compensation complex to X-linked target genes

Genes & Development (2007)

Jop Kind Asifa Akhtar

Dosage compensation is a process required to balance the expression of X-linked genes between males and females. In Drosophila this is achieved by targeting the dosage compensation complex or the male-specific lethal (MSL) complex to the male X chromosome. In order to study the mechanism of targeting, we have studied two X-chromosomal genes, mof and CG3016 , using chromatin immunoprecipitation as well as immuno-FISH analysis on transgenic flies. We show that MSL complex recruitment requires the genes to be in a transcriptionally active state. MSL complex recruitment is reversible because blocking transcription severely reduces MSL binding to its target genes. Furthermore, targeting cues are found toward the 3′ end of the gene and depend on the passage of the transcription machinery through the gene, whereby the type of promoter and the direction of transcription are dispensable. We propose a model of dynamic MSL complex binding to active genes based on exposed DNA target elements.

Dosage compensation

Transcription

Chromatin immunoprecipitation

Gene dosage

10.1101/gad.430807

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Citations (62)

The CD27 and CD70 Costimulatory Pathway Inhibits Effector Function of T Helper 17 Cells and Attenuates Associated Autoimmunity

Immunity (2012)

Jonathan M. Coquet Sabine Middendorp Gerda Horst Jop Kind Elise A. M. Veraar

Interleukin-23

ZAP70

10.1016/j.immuni.2012.09.009

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Citations (100)

Attach and stretch: Emerging roles for genome–lamina contacts in shaping the 3D genome

Current Opinion in Cell Biology (2020)

Pim M. J. Rullens Jop Kind

A large proportion of the metazoan genome is spatially segregated at the nuclear periphery through genomic contacts with the nuclear lamina, a thin meshwork of lamin filaments that lines the inner-nuclear membrane. Lamina-associated domains are believed to contribute to the regulation of gene transcription and to provide structural three-dimensional support to the organization of the genome in A and B compartments and topologically associating domains. In this review, we will evaluate recent work addressing the role of lamina-associated domains in three-dimensional genome organization and propose experimental frameworks that may expand our understanding of their interdependence.

Nuclear lamina

Genomic Organization

Lamina

Inner membrane

10.1016/j.ceb.2020.11.006

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Citations (22)

Time-resolved and multifactorial profiling in single cells resolves the order of heterochromatin formation events during X-chromosome inactivation

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Samy Kefalopoulou Pim M. J. Rullens Kim L. de Luca Sandra S. de Vries Tessy Korthout

The regulation of gene expression is governed at multiple levels of chromatin organization. However, how coordination is achieved remains relatively unexplored. Here we present Dam&ChIC, a method that enables time-resolved and multifactorial chromatin profiling at high resolution in single cells. Analysis of genome-lamina interactions in haploid cells reveals highly dynamic spatial repositioning of small domains during interphase and partial inheritance over mitosis. Dam&ChIC applied to study random X-inactivation uncovers that spreading of H3K27me3 on the inactive X chromosome (Xi) overlaps with remarkable genome-lamina detachment. We find that genome-lamina detachment precedes H3K27me3 accumulation on the Xi and occurs upon mitotic exit. Domains that retain genome-lamina interactions are marked by high pre-existing H3K9me3 levels. These findings imply an important role for genome-lamina interactions in regulating H3K27me3 accumulation on the Xi. We anticipate that Dam&ChIC will be instrumental in unraveling the interconnectivity and order of chromatin events underlying cell-state changes in single cells.

Interphase

Nuclear lamina

Replication timing

10.1101/2023.12.15.571749

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Citations (6)

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

Nature Genetics (2024)

Isabel Guerreiro Franka J. Rang Yumiko Kawamura Carla Kroon-Veenboer Jeroen Korving

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.

Nuclear lamina

Totipotent

Genomic Organization

Spatial organization

10.1038/s41588-024-01902-8

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Citations (2)

DamC reveals principles of chromatin folding in vivo without crosslinking and ligation

Nature Structural & Molecular Biology (2019)

Josef Redolfi Yinxiu Zhan Christian Valdes‐Quezada Mariya Kryzhanovska Isabel Guerreiro

CTCF

Chromosome conformation capture

10.1038/s41594-019-0231-0

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Citations (80)

Constitutive nuclear lamina–genome interactions are highly conserved and associated with A/T-rich sequence

Genome Research (2012)

Wouter Meuleman Daan Peric‐Hupkes Jop Kind Jean–Bernard Beaudry Ludo Pagie

In metazoans, the nuclear lamina is thought to play an important role in the spatial organization of interphase chromosomes, by providing anchoring sites for large genomic segments named lamina-associated domains (LADs). Some of these LADs are cell-type specific, while many others appear constitutively associated with the lamina. Constitutive LADs (cLADs) may contribute to a basal chromosome architecture. By comparison of mouse and human lamina interaction maps, we find that the sizes and genomic positions of cLADs are strongly conserved. Moreover, cLADs are depleted of synteny breakpoints, pointing to evolutionary selective pressure to keep cLADs intact. Paradoxically, the overall sequence conservation is low for cLADs. Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this “A/T rule” in embryonic stem cells, but not in differentiated cells. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level. Taken together, these results reveal that the spatial organization of mammalian genomes is highly conserved and tightly linked to local nucleotide composition.

Nuclear lamina

Synteny

Lineage (genetic)

10.1101/gr.141028.112

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Citations (431)

A pendulum of induction between the epiblast and extra-embryonic endoderm supports post-implantation progression

Development (2022)

Erik Vrij Yvonne Scholte op Reimer Laury Roa Fuentes Isabel Guerreiro Viktoria Holzmann

Embryogenesis is supported by dynamic loops of cellular interactions. Here, we create a partial mouse embryo model to elucidate the principles of epiblast (Epi) and extra-embryonic endoderm co-development (XEn). We trigger naive mouse embryonic stem cells to form a blastocyst-stage niche of Epi-like cells and XEn-like cells (3D, hydrogel free and serum free). Once established, these two lineages autonomously progress in minimal medium to form an inner pro-amniotic-like cavity surrounded by polarized Epi-like cells covered with visceral endoderm (VE)-like cells. The progression occurs through reciprocal inductions by which the Epi supports the primitive endoderm (PrE) to produce a basal lamina that subsequently regulates Epi polarization and/or cavitation, which, in return, channels the transcriptomic progression to VE. This VE then contributes to Epi bifurcation into anterior- and posterior-like states. Similarly, boosting the formation of PrE-like cells within blastoids supports developmental progression. We argue that self-organization can arise from lineage bifurcation followed by a pendulum of induction that propagates over time.

Epiblast

10.1242/dev.192310

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Citations (18)

Genome-wide profiling of DNA repair proteins in single cells

Nature Communications (2024)

Kim L. de Luca Pim M. J. Rullens Magdalena A. Karpińska Sandra S. de Vries Agnieszka Gacek‐Matthews

Accurate repair of DNA damage is critical for maintenance of genomic integrity and cellular viability. Because damage occurs non-uniformly across the genome, single-cell resolution is required for proper interrogation, but sensitive detection has remained challenging. Here, we present a comprehensive analysis of repair protein localization in single human cells using DamID and ChIC sequencing techniques. This study reports genome-wide binding profiles in response to DNA double-strand breaks induced by AsiSI, and explores variability in genomic damage locations and associated repair features in the context of spatial genome organization. By unbiasedly detecting repair factor localization, we find that repair proteins often occupy entire topologically associating domains, mimicking variability in chromatin loop anchoring. Moreover, we demonstrate the formation of multi-way chromatin hubs in response to DNA damage. Notably, larger hubs show increased coordination of repair protein binding, suggesting a preference for cooperative repair mechanisms. Together, our work offers insights into the heterogeneous processes underlying genome stability in single cells. Accurate repair of DNA damage is crucial for genome stability and preventing disease. Here, the authors adapt single-cell omics technologies to map the location of repair proteins across the human genome, showing formation of multi-way chromatin hubs in response to damage.

10.1038/s41467-024-54159-4

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Citations (1)

Simultaneous quantification of protein–DNA contacts and transcriptomes in single cells

Nature Biotechnology (2019)

Koos Rooijers Corina M. Markodimitraki Franka J. Rang Sandra S. de Vries Alex Chialastri

Polycomb-group proteins

10.1038/s41587-019-0150-y

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Citations (100)