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bioRxiv2026

Complex temperature profiles recorded through antisense co-transcriptional sensitivity

Plants integrate widely fluctuating temperature over seasons to regulate their development. In vernalization, FLOWERING LOCUS C (FLC) is repressed by cold-induced antisense (COOLAIR) transcription and epigenetically silenced by Polycomb (PRC2) epigenetic switching. Here, we show how COOLAIR co-transcriptional dynamics are central to integrating different facets of the natural temperature profile over different timescales. Constant cold alters COOLAIR RNA polymerase II processivity, splicing and polyadenylation site choice with distinct kinetics over days to weeks. In contrast, fluctuations below freezing at the same mean temperature caused extensive premature termination and chromatin retention of COOLAIR. High-resolution chromatin contact mapping showed COOLAIR premature termination altered local chromatin topology. This enhanced FLC promoter-gene body contacts, coincident with H3K4me1 loss and reduced FLC transcription. Multiple features of COOLAIR co-transcriptional sensitivity therefore act as thermosensory antennae, integrating distinct facets of winter temperature through local chromatin regulation, to robustly repress FLC in natural conditions.

plant biology↗

bioRxiv2020

The regulation of mammalian maternal-to-embryonic transition by Eukaryotic translation initiation factor 4E

Genetic and inhibitor studies show expression of eukaryotic translation initiation factor 4E (eIF4E) was required for the successful maternal-to-embryonic transition of mouse embryos. eIF4E was in both gametes and in the cytoplasm and pro-nuclei soon after fertilization, and at each stage of early development. Knockout (Eif4e-/-) by PiggyBac (PB) [Act-RFP] transposition caused peri-implantation embryonic lethality due to the failure of embryos to form a pluripotent epiblast. Maternal stores of eIF4E supported development up to the 2-4-cell stage after which new expression occurred from both alleles. Inhibition of the maternally acquired stores of eIF4E (4EGI-1 inhibitor) resulted in a developmental block at the 2-4-cell stage. 4E-BP1 is a hypophosphorylation-dependent negative regulator of eIF4E. mTOR activity was required for 4E-BP1 phosphorylation and inhibiting 4EGI-1 retarded embryo development. eIF4E expression and activity is regulated at key embryonic transitions in the mammalian embryo and is essential for successful transition to embryonic control of development. Significance StatementeIF4E is recognized as the rate-limiting factor for CAP-dependent translation. This work used a combination of a gene knockout model, selective pharmacological inhibition and expression analyses to investigate the expression and function of Eif4e in the early mouse embryo. It provides compelling evidence for the essential role of Eif4E in the normal processes of early mammalian embryo development, including the formation of the pluripotent epiblast and the maternal-embryonic transition. The unexpected evidence for a growth deficit in mice hypomorphic for Eif4e will be a key area of future investigation. It also provides for the first time a powerful demonstration of the utility of the PB [Act-RFP] transposon mouse model for analyzing the molecular regulation of early mammalian embryo development.

developmental biology↗