Biology subjects

Belmonte, T.

Publications and source records attributed to Belmonte, T..

2 recordsLinked to original sources

bioRxiv2019

Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. We meta-analyzed the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (7 studies, N=1700, 344 with any MSDP). We identified 1224 CpGs that were associated with MSDP, of which 341 associated with birth outcomes and 141 associated with gene expression. Only 6 of these CpGs were consistent with the findings from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP associated CpGs were enriched for growth-factor signaling, hormone activity, inflammation, and vascularization, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.

genomics↗

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↗