Zygotic genome activation (ZGA) is a universal process in early embryogenesis of metazoan, when the quiescent zygotic nucleus initiates global transcription. However, the mechanisms related to massive genome activation and allele-specific expression (ASE) remain not well understood. Here, we develop hybrids from two deeply diverged (120 Mya) ascidian species to symmetrically document the dynamics of ZGA. We identify two coordinated ZGA waves represent early developmental and housekeeping gene reactivation, respectively. Single-cell RNA sequencing reveals that the major expression wave exhibits spatial heterogeneity and significantly correlates with cell fate. Moreover, allele-specific expression occurs in a species- rather than parent-related manner, demonstrating the divergence of cis-regulatory elements between the two species. These findings provide insights into ZGA in chordates.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944513PMC
http://dx.doi.org/10.1038/s41467-024-46780-0DOI Listing

Publication Analysis

Top Keywords

allele-specific expression
12
genome activation
12
zygotic genome
8
temporospatial hierarchy
4
hierarchy allele-specific
4
expression
4
expression zygotic
4
activation revealed
4
revealed distant
4
distant interspecific
4

Similar Publications

Inactivation of disease alleles by allele-specific editing is a promising approach to treat dominant-negative genetic disorders, provided the causative gene is haplo-sufficient. We previously edited a dominant missense mutation with inactivating frameshifts and rescued disease-relevant phenotypes in induced pluripotent stem cell (iPSC)-derived motor neurons. However, a multitude of different missense mutations cause disease.

View Article and Find Full Text PDF

KDM6A facilitates Xist upregulation at the onset of X inactivation.

Biol Sex Differ

January 2025

Department of Laboratory Medicine and Pathology, School of Medicine, University of Washington, Seattle, WA, 98195, USA.

Background: X chromosome inactivation (XCI) is a female-specific process in which one X chromosome is silenced to balance X-linked gene expression between the sexes. XCI is initiated in early development by upregulation of the lncRNA Xist on the future inactive X (Xi). A subset of X-linked genes escape silencing and thus have higher expression in females, suggesting female-specific functions.

View Article and Find Full Text PDF

Systematic functional characterization of non-coding regulatory SNPs associated with central obesity.

Am J Hum Genet

January 2025

Key Laboratory of Biomedical Information Engineering of Ministry of Education, Key Laboratory of Biology Multiomics and Diseases in Shaanxi Province Higher Education Institutions, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, Shaanxi, China. Electronic address:

Central obesity is associated with higher risk of developing a wide range of diseases independent of overall obesity. Genome-wide association studies (GWASs) have identified more than 300 susceptibility loci associated with central obesity. However, the functional understanding of these loci is limited by the fact that most loci are in non-coding regions.

View Article and Find Full Text PDF

G6PC2 controls glucagon secretion by defining the set point for glucose in pancreatic α cells.

Sci Transl Med

January 2025

Institute of Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Elevated glucagon concentrations have been reported in patients with type 2 diabetes (T2D). A critical role for α cell-intrinsic mechanisms in regulating glucagon secretion was previously established through genetic manipulation of the glycolytic enzyme glucokinase (GCK) in mice. Genetic variation at the glucose-6-phosphatase catalytic subunit 2 () locus, encoding an enzyme that opposes GCK, has been reproducibly associated with fasting blood glucose and hemoglobin A1c.

View Article and Find Full Text PDF

Different sheep breeds show distinct phenotypic plasticity in fat deposition in the tails. The genetic background underlying fat deposition in the tail of sheep is complex, multifactorial, and may involve allele-specific expression (ASE) mechanism to modulate allelic expression. ASE is a common phenomenon in mammals and refers to allelic imbalanced expression modified by cis-regulatory genetic variants that can be observed at heterozygous loci.

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!