Dataset Information

Time-Resolved Analysis Reveals FEN1 as a Crucial Factor of Circadian Transcriptome Dynamics and Core Cellular Homeostasis in HEK 293T cell

ABSTRACT: Circadian rhythms orchestrate genome-wide transcriptional oscillations to coordinate cellular homeostasis. While the core clock machinery has been extensively characterized, its integration with other critical biological processes, such as the DNA damage response and cell cycle control, remains incompletely understood. Here, we identify the DNA replication and repair nuclease FEN1 as a critical modulator of circadian transcriptome dynamics in human cells. Time-series RNA-seq across six circadian time points in synchronized HEK293T cells revealed that FEN1 depletion induces widespread reprogramming of rhythmic gene expression, with over 30% of oscillatory transcripts exhibiting loss or gain of rhythmicity, phase shifts, or amplitude changes. Notably, reprogrammed genes were enriched in cell cycle, DNA damage response, and cellular senescence pathways. Systematic phase set enrichment analysis uncovered coordinated delays and inversions in G1/S checkpoint regulators and metabolic genes, disrupting temporal coherence. Despite retention of rhythmicity in core clock genes, amplitude attenuation and phase advances were observed, indicating compromised oscillatory stability. Functional validation demonstrated reduced S phase entry, G1 accumulation, and accelerated senescence in FEN1 knockdown cells, in line with transcriptomic predictions. qPCR analysis confirmed altered expression of representative target genes. These findings uncover an unrecognized role for FEN1 in sustaining circadian transcriptional architecture and reveal its broader impact on cell cycle control and aging programs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE308811 | GEO | 2026/03/04

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background Dysfunction of the circadian clock has been implicated in the pathogenesis of a variety of diseases, including metabolic disorders, inflammatory conditions, and cancer. While the significance of circadian rhythm in diabetic nephropathy is gaining attention, the specific alterations in circadian profiles in diabetic nephropathy remain unexplored. Methods In the present study, we performed RNA sequencing on renal cortex samples collected every 4-hour across the day from both control and diabetic mice. The rhythmicity of genes was identified using the JTK_CYCLE algorithm for each group. Genes that lost, acquired, or sustained rhythmicity in diabetic mice were denoted the circadian dysregulation gene-set. Subsequent bioinformatic analyses focused on this gene set to investigate the circadian reprogramming in diabetic nephropathy. Results We observed significant circadian disruption in the kidney of diabetic mice, marked by both the gain and loss of rhythmicity, along with alterations in the phase and amplitude of genes that retained rhythmic expressions. Circadian disturbances such like phase shifts and alterations in relative amplitude or mesor, were noted in core clock genes. Furthermore, genes that lost rhythmicity in diabetic nephropathy were predominantly associated with protein homeostasis and glycolipid metabolism, whereas those that gained rhythmicity were mainly linked to gene regulation, fatty acid metabolism, and protein transport. The genes in the circadian dysregulation gene-set that exhibit differential expression at least at one Zeitgeber time, were most prominently enriched in lipid metabolic process. WGCNA and correlation analysis revealed co-expression networks involving core clock genes and PPAR signaling pathway with renal triglyceride levels. Conclusions Our study reveals substantial circadian disruption in diabetic nephropathy, with significant impacts on protein homeostasis and glycolipid metabolism. Furthermore, our findings highlight the potential influence of circadian system dysregulation on the disorder of fatty acid metabolism in diabetic nephropathy.

Dataset Information

Time-Resolved Analysis Reveals FEN1 as a Crucial Factor of Circadian Transcriptome Dynamics and Core Cellular Homeostasis in HEK 293T cell

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets