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Unveiling the Dynamics of LAD Reorganization and Transcription in Early Embryonic Development


In a recent publication in Genes and Development, the researchers from Torres-Padilla lab (Institute of Epigenetics and Stem Cells, IES) have shed light on the intricate interplay between nuclear organization and transcriptional activity during early embryonic development.

In the complex process of embryonic development, an intriguing relationship is established between transcriptional activity and nuclear architecture. In particular, the lamina-associated domains (LADs) are reshaped in the early stages of mammalian embryonic development and their establishment is associated with the transcriptional activity. Fertilization paves the way for the development of an embryo and triggers a dynamic reorganization of LADs during the initial stages of embryogenesis. However, a pivotal question arises during the second cell cycle of development, a crucial turning point, as the embryo transitions from relying on maternal factors to initiating its own transcriptional program (known as zygotic genome activation or ZGA). But which comes first, the reorganization of LADs or transcription? And, do LADs and transcription influence each other?

Researchers have employed the LaminB1-DamID technique to map LADs and inter-LADs (iLADs). While many LADs remain unchanged between the zygote and 2-cell stage, the picture becomes clearer when focusing on genes activated at ZGA specifically. Remarkably, some of the ZGA genes undergo spatial changes, detaching from the nuclear periphery as the 2-cell stage progresses. To investigate directly the connection between transcription and LAD reshaping, the researchers inhibited transcription, and consequently ZGA. Upon inhibition, the researchers found that the nuclear architecture undergoes dramatic changes at the 2-cell stage. In particular, LADs exhibited a reduction in AT-richness compared to iLADs, highlighting changes in their compositional makeup. Interestingly, LADs also underwent shifts in retrotransposon content, becoming depleted from LINEs and concurrently enriched in SINEs, despite the fact that these elements remain transcriptionally inactive. Additionally, the researchers focus on the epigenetic mark H3K4me3, conventionally associated with active transcription.. Inhibition of transcription led to the repositioning of H3K4me3 within LADs, while correspondingly reducing its presence in iLADs, effectively reversing the typical pattern observed in control embryos. These findings underscore the intricate interplay between transcriptional activity and the dynamic reorganization of nuclear territories, offering crucial insights into early embryonic development.

In conclusion, the Pal et al., have shed light on the intricate interplay between nuclear organization and transcriptional activity during early embryonic development. Their work underscore the decisive role of ZGA as the embryo takes the reins of its own destiny and emphasizes the dynamic nature of LADs and their connection to gene expression.

To read the full publication, please go here