It is well known that the chromatin states play a major role in cell-fate decision and cell-identity maintenance; however, the spatial variation of chromatin states remains poorly characterized. Here, by leveraging recently available spatial-CUT&Tag data, we systematically characterized the global spatial organization of the H3K4me3 profiles in a mouse embryo. Our analysis identified a subset of genes with spatially coherent H3K4me3 patterns, which together delineate the tissue boundaries. The spatially coherent genes are strongly enriched with tissue-specific transcriptional regulators. Remarkably, their corresponding genomic loci are marked by broad H3K4me3 domains, which is distinct from the typical H3K4me3 signature. Spatial transition across tissue boundaries is associated with continuous shortening of the broad H3K4me3 domains as well as expansion of H3K27me3 domains. Our analysis reveals a strong connection between the genomic and spatial variation of chromatin states, which may play an important role in embryonic development.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10760050PMC
http://dx.doi.org/10.1101/2023.12.11.570452DOI Listing

Publication Analysis

Top Keywords

broad h3k4me3
12
chromatin states
12
embryonic development
8
states play
8
spatial variation
8
variation chromatin
8
spatially coherent
8
tissue boundaries
8
h3k4me3 domains
8
spatial
5

Similar Publications

H3K4me3 Genome-Wide Distribution and Transcriptional Regulation of Transposable Elements by RNA Pol2 Deposition.

Int J Mol Sci

December 2024

Jiangsu Livestock Embryo Engineering Laboratory, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.

Zygotic genome activation (ZGA) is critical for early embryo development and is meticulously regulated by epigenetic modifications. H3K4me3 is a transcription-permissive histone mark preferentially found at promoters, but its distribution across genome features remains incompletely understood. In this study, we investigated the genome-wide enrichment of H3K4me3 during early embryo development and embryonic stem cells (ESCs) in both sheep and mice.

View Article and Find Full Text PDF

The dynamics of three-dimensional (3D) genome organization are essential to transcriptional regulation. While enhancers regulate spatiotemporal gene expression, chromatin looping is a means for enhancer-promoter interactions yielding cell-type-specific gene expression. Further, non-canonical DNA secondary structures, such as G-quadruplexes (G4s), are related to increased gene expression.

View Article and Find Full Text PDF

ZBTB7A is a modulator of KDM5-driven transcriptional networks in basal breast cancer.

Cell Rep

December 2024

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA 02142, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; The Ludwig Center at Harvard, Boston, MA 02115, USA. Electronic address:

Article Synopsis
  • The study identifies KDM5A as an important oncogene in basal breast cancer, showing that its amplification and overexpression can be targeted to suppress cancer cell growth.
  • CRISPR knockout screens reveal that deleting the ZBTB7A transcription factor makes cells more sensitive to KDM5 inhibition, while the deletion of RHO-GTPases provides resistance.
  • The research highlights the role of ZBTB7A and KDM5A/B in regulating gene expression, particularly regarding NF-κB targets, and links high ZBTB7A levels to poorer treatment responses in triple-negative breast cancer.
View Article and Find Full Text PDF

Systematic analysis identifies a connection between spatial and genomic variations of chromatin states.

Cell Syst

November 2024

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address:

Chromatin states play important roles in the maintenance of cell identities, yet their spatial patterns remain poorly characterized at the organism scale. We developed a systematic approach to analyzing spatial epigenomic data and then applied it to a recently published spatial-CUT&Tag dataset that was obtained from a mouse embryo. We identified a set of spatial genes whose H3K4me3 patterns delineate tissue boundaries.

View Article and Find Full Text PDF

The nuclear genome is spatially organized into a three-dimensional (3D) architecture by physical association of large chromosomal domains with subnuclear compartments including the nuclear lamina at the radial periphery and nuclear speckles within the nucleoplasm. However, how spatial genome architecture regulates human brain development has been overlooked owing to technical limitations. Here, we generate high-resolution maps of genomic interactions with the lamina and speckles in cells of the neurogenic lineage isolated from midgestational human cortex, uncovering an intimate association between subnuclear genome compartmentalization, chromatin state and transcription.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!