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The exact relationship between 3D chromatin interactions and enhancer function is unclear. By probing three-dimensional enhancer interactions in developing embryos, two studies now show nuanced dynamics in tissue-specific contexts and reveal how moderately increased enhancer–promoter interactions coincide with functionality.
In mice, zygotic genome activation occurs at onset of the two-cell stage in embryonic development and coincides with the exit from totipotency. Our work shows that the transcription factor DUXBL participates in silencing part of the stage-specific two-cell-associated transcriptional program and is required for development to proceed.
We show that in addition to promoter activation, MYC drives cancer progression by activating transcriptional enhancers via a distinct mechanism. MYC cooperates with several other proteins at these cis-regulatory regions to change the epigenome and promote recruitment of RNA polymerase II and enhancer transcription.
Mutational signatures help to deconvolve the different processes that shape cancer genomes. A new tool now alleviates some of the persistent challenges in the field.
Genome-wide CRISPR screening coupled with ATAC-see uncovered modulators that influence global chromatin accessibility. Notably, TFDP1 emerged as a pivotal modulator of chromatin accessibility that acts by controlling histone transcription. Depletion of TFDP1 induced a global elevation in accessibility, enhancing the efficiency of genome editing and iPS cell reprogramming.
Gestational diabetes is a complex metabolic condition thought to have a strong genetic predisposition. A large genome-wide association study of participants from Finland sheds light on the genetic contributors, opening avenues for research into mechanisms that underlie glucose regulation in pregnancy to improve the health of mothers and babies.
Spatial omics enables the molecular profiling of cells with the tissue context preserved. A new analytic approach shows how cellular neighborhood analysis and feature augmentation can spatially connect and cluster millions of cells into higher-order functional units.
We constructed a pan-genome using 27 high-quality representative Brassica oleracea genomes. Using this pan-genome, together with multi-omics datasets from large-scale populations, we uncovered the important role of structural variations as dosage regulators of gene expression, which drives the morphotype diversification in B. oleracea.
A common architectural feature of the genome in many organisms is chromatin domains. A synthetic biology approach now builds chromatin domains from scratch and identifies some of the minimal components needed for their formation.
An open-source automated algorithm called DeepFlow enables large-scale derivation of aortic flow measurements, and genetic analysis of aortic flow, structural and functional traits demonstrates a causal relationship between aortic size and aortic valve regurgitation.
Understanding clinical heterogeneity in attention deficit hyperactivity disorder (ADHD) is important for improving personalized care and long-term outcomes. A study exploits the large scale and breadth of phenotyping of the iPSYCH cohort to link clinical heterogeneity to genetic heterogeneity in ADHD.
This Review explores mechanistic theories of aging, discusses challenges in establishing causality of these mechanisms and suggests that genetically informed investigation will help address this gap.
Skin color is highly variable in Africans, but the underlying molecular mechanisms remain poorly understood. Using population genetics and functional genomics, we identified key genetic variants, regulatory elements and genes that affect skin pigmentation, an adaptive trait, which provides valuable insights into the mechanisms underlying human skin color diversity and evolution.
The genetic background of pediatric acute myeloid leukemia (AML) does not fit with classification systems developed for adult AML. This study investigates the genetic background of pediatric AML and proposes a genomic framework for improved classification and risk stratification based on the driver alterations.
