Articles in 2021

Chromothripsis, a chromosomal shattering event, can be elicited by micronuclei and chromosome bridges formed by CRISPR–Cas9-generated double-stranded breaks. Extensive chromosomal rearrangements may thus be an on-target effect of genome editing.

Whole-genome resequencing of 445 Lactuca accessions, including major lettuce crop types and wild relative species, provides a comprehensive map of lettuce genome variations and sheds light on the domestication history of cultivated lettuce.

Cells resembling human fetal adrenal neuroblasts have been identified as major neuroblastoma cancer cells through single-cell mRNA comparison. Tumor risk stratification correlates with the differentiation of neuroblast-like neuroblastoma cells.

Case–case genome-wide association studies (GWAS) within a single genotyped cohort have proven useful in identifying genetic variants explaining different health outcomes, yet they are limited by data availability. A new study by Peyrot and Price proposes a clever statistical method to overcome this problem by inferring case–case GWAS results from a pair of standard case–control GWAS summary statistics that need not be from the same cohort.

Guided Open Access is a new publishing option offered at Nature Genetics. Authors can submit once and be simultaneously considered by three journals. Editorial collaboration and a single submission system combine to make the publication process easier and faster.

The International Mouse Phenotyping Consortium reports the generation of new mouse mutant strains for more than 5,000 genes, including 2,850 novel null, 2,987 novel conditional-ready and 4,433 novel reporter alleles.

MPHOSPH8 loss inhibits acute myeloid leukemia (AML) development by reactivating LINE-1 retrotransposons. LINE-1 suppression is associated with therapy resistance and poor prognosis in patients with AML.

Single-cell transcriptome profiling of human embryonic sympathoadrenal tissues identifies developmental transitions and suggests that intra-adrenal sympathoblasts arising from Schwann cell precursors are a potential neuroblastoma cell of origin.

Polycomb-group proteins assemble into two primary complexes—Polycomb repressive complex (PRC) 1 and 2—that safeguard cell fate by repressing gene transcription. Two new studies explore the PRC1 landscape during the transition from gametes to embryos in mice, thus providing insight into the intergenerational transmission of epigenetic information and gene regulation dynamics as embryos prepare for gastrulation.

H2AK119ub1 and H3K27me3 have different genome-wide dynamics in mouse preimplantation embryos. Loss of H2AK119ub1, but not H3K27me3, causes premature activation of developmental genes during zygotic genome activation.

A multivariate genome-wide association study highlighting loci that influence both face and brain shape suggesting shared developmental axes during early embryogenesis. These loci did not overlap with those governing behavioral–cognitive traits or neuropsychiatric risk indicating divergence between early brain development and cognitive function.

In early mouse embryos, PRC1-mediated H2AK119ub1 deposition precedes H3K27me3. Deficiency in variant PRC1 reduces H2AK119ub1 and leads to gene-selective loss of H3K27me3 in oocytes, which is inherited by embryos.

Extremely conserved 5′ UTRs act as cis-regulatory elements, playing an unsuspected role in translation regulation. A new in-cell mutational method, icM², shows that these 5′ UTRs adopt alternative structures that depend on RNA helicase activity.

The structure of chromatin is associated with its function, but precisely how is unclear. New data show that the higher-order architecture of the genome is similar among cell types with widely variant fates and gene expression patterns, thus challenging the view that chromatin domains determine function in the genome.

Chromatin conformation is largely independent of dorsoventral gene expression during early embryonic development in Drosophila. Despite tissue-specific differences in chromatin state and gene expression, three-dimensional chromatin organization is maintained across tissues.

Single-cell ATAC-seq analysis of human pancreatic islet cells identifies different cell clusters and transcription factors that underlie lineage- and state-specific regulation and helps prioritize type 2 diabetes risk variants.

Single-cell analysis of Drosophila development with Hi-M suggests that physical proximity between regulatory regions does not necessarily instruct transcriptional states. Multi-way analyses identify the existence of regulatory hubs that emerge before topologically associating domains.

Stretches of non-coding DNA that have remained identical across millions of years of evolution are typically assumed to have functional regulatory roles that would be compromised by any amount of nucleotide substitution. A new study finds that these ultraconserved regions are more robust to mutagenesis than their level of conservation would suggest.

Immune responses require a delicate balance: a weak response can cause immunodeficiency, whereas an excessive response can lead to hyperinflammatory disease and hematological malignancy. Because spleen tyrosine kinase has roles in multiple signaling pathways, its gain-of-function alterations in humans cause hypogammaglobulinemia as well as autoinflammation and predisposition to B cell lymphoma.