Chromatin Level Epigenetic Reprogramming and Altered Transcriptional Dynamics by lncRNAs uc.123 and uc.382 Links Early Life Stress to Depression Vulnerability [ChIRP-Seq ELS]

ABSTRACT: Early Life Stress (ELS) refers to exposure to adverse childhood experiences such as neglect, abuse, or parental separation. These stressors can disrupt brain development and increase susceptibility to psychiatric disorders, including major depressive disorder (MDD). Recent evidence suggests that these effects are mediated by transcriptional regulation and may be driven by epigenetic processes, including chromatin reorganization. Long non-coding RNAs (lncRNAs), which are highly expressed in the brain, have emerged as key modulators of these epigenetic processes. Using maternal separation (MS) as an early-life stress model, differential expression of uc.123, uc.382, uc.429 and uc.104 was noted, with significant upregulation observed for uc.123 and uc.382 in the prefrontal cortex (PFC) of MS rats. Genome-wide chromatin mapping using chromatin isolation by RNA purification sequencing (ChIRP-seq) demonstrated that the lncRNAs uc.123 and uc.382 were associated with chromatin regions and subsequent gene regulation. Integration with PFC RNA-seq results highlighted that uc.123 and uc.382 regulate distinct yet functionally complementary gene networks. Chromatin binding by uc.123 and uc.382 in ELS rats differentially regulated genes involved in synaptic plasticity and neuroinflammation. Chromatin immunoprecipitation (ChIP)-qPCR for H3K27ac displayed increased chromatin accessibility at key target loci of uc.123 and uc.382. This further supports their role in modulating histone marks and gene transcription under MS. Altogether, our results demonstrate that ELS induce persistent transcriptional changes via lncRNA-mediated chromatin remodeling. These findings provide new insights into how ELS induces long-lasting transcriptional and epigenetic changes, advancing our understanding of the molecular basis of stress-related neuropathology.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE344336 | GEO | 2026/08/24

REPOSITORIES: GEO