Biology subjects

Urdinguio, R. G.

Publications and source records attributed to Urdinguio, R. G..

3 recordsLinked to original sources

bioRxiv2024

Age-Dependent Maturation and Rejuvenation of the Neural 3D Chromatin Interactome in Enriched Environments

Aging is a multifactorial biological process resulting in physiological and cellular decline. However, our understanding of age-related changes in 3D genome organization and the effect of external interventions on this process, remains limited. Here we describe alterations in the landscape of the 3D chromatin interactome upon aging, utilizing the low input Promoter Capture Hi-C (liCHi-C) technique with hippocampal neurons. We integrated liCHi-C data with RNA-seq data to identify functional implications. Furthermore, we assessed the effect of exposure to environmental enrichment (EE). Remarkably, our results demonstrated an age- dependent modulation of promoter interactions and expression with EE, with aging-like changes induced in young mice upon EE, likely associated with early brain maturation; while age-related alterations were reverted in old mice, leading to a partial rejuvenation of aged mouse hippocampi. These findings revealed a dynamic behaviour of the neuronal 3D chromatin structure over time, which can be modulated by external interventions.

genomics↗

bioRxiv2022

Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming

The expression of the pluripotency factors OCT4, SOX2, KLF4 and MYC (OSKM) can convert somatic differentiated cells into pluripotent stem cells in a process known as reprogramming. Notably, cycles of brief OSKM expression do not change cell identity but can reverse markers of aging in cells and extend longevity in progeroid mice. However, little is known about the mechanisms involved. Here, we have studied changes in the DNA methylome, transcriptome and metabolome in naturally aged mice subject to a single period of transient OSKM expression. We found that this is sufficient to reverse DNA methylation changes that occur upon aging in the pancreas, liver, spleen and blood. Similarly, we observed reversion of transcriptional changes, especially regarding biological processes known to change during aging. Finally, some serum metabolites altered with aging were also restored to young levels upon transient reprogramming. These observations indicate that a single period of OSKM expression can drive epigenetic, transcriptomic and metabolomic changes towards a younger configuration in multiple tissues and in the serum.

cell biology↗

bioRxiv2017

Non-canonical aberrant DNA hypermethylation in glioma

Aberrant DNA hypermethylation is a hallmark of cancer although the underlying molecular mechanisms are still poorly understood. To study the possible role of 5-hydroxymethylcytosine (5hmC) in this process we analyzed the global and locus-specific genome-wide levels of 5hmC in primary samples from 54 gliomas and 72 colorectal cancer patients. Levels of 5hmC in colorectal cancer were very low and no consistent changes were detected between control tissues and tumors. As expected, levels of 5hmC in non-tumoral brain samples were high and significantly reduced at the 49,601 CpG sites in gliomas. Strikingly, hypo-hydroxymethylation at 4,627 (9.3%) of these CpG sites was associated with aberrant DNA hypermethylation. The DNA regions containing these CpG sites were enriched in H3K4me2, and presented a different genuine chromatin signature to that characteristic of the genes classically aberrantly hypermethylated in cancer. We conclude that this data identifies a novel 5hmC-dependent non-canonical class of aberrant DNA hypermethylation in glioma.

cancer biology↗