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

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.