@misc{10481/79295,
year = {2022},
month = {12},
url = {https://hdl.handle.net/10481/79295},
abstract = {Objective: To assess the genetic and epigenetic effects promoted by Bisphenol A (BPA) exposure in adolescent
males from the Spanish INMA-Granada birth cohort, and in human cells.
Methods: DNA methylation was analysed using MEDIP. Repeat number variation in genomic DNA was evaluated,
along with the analysis of H3K4me3 by using chromatin immunoprecipitation followed by high-throughput sequencing
(ChIP-seq). Analyses were performed with material extracted from whole blood of the adolescents, complemented
by in vitro assessments of human (HeLa) cells exposed to 10 nM BPA, specifically, immunofluorescence
evaluation of protein levels, gene expression analysis and ChIP‒qPCR analysis.
Results: Adolescents in the high urinary BPA levels group presented a higher level of Satellite A (SATA) repetitive
region copy numbers compared to those in the low BPA group and a tendency towards increase in telomere length.
We also observed decreased DNA methylation at the promoters of the imprinted genes H19, KCNQ1, and IGF2; at
LINE1 retroelements; and at the ARID2, EGFR and ESRRA and TERT genes. Genome-wide sequencing revealed increased
H3K4me3 occupancy at the promoters of genes encoding histone acetyltransferases, telomeric DNA binding factors
and DNA repair genes. Results were supported in HeLa cells exposed to 10 nM BPA in vitro. In accordance with
the data obtained in blood samples, we observed higher H3K4me3 occupancy and lower DNA methylation at some
specific targets in HeLa cells. In exposed cells, changes in the expression of genes encoding DNA repair factors (ATM,
ARID2, TRP53) were observed, and increased expression of several genes encoding telomeric DNA binding factors (SMG7, TERT, TEN1, UPF1, ZBTB48) were also found. Furthermore, an increase in ESR1/ERa was observed in the nuclei of
HeLa cells along with increased binding of ESR1 to KAT5, KMT2E and TERF2IP promoters and decreased ESR1 binding
at the RARA promoter. The DNA damage marker p53/TP53 was also increased.
Conclusion: In this pilot study, genome-wide analysis of histone trimethylation in adolescent males exposed to BPA
revealed a global impact on the expression of genes encoding telomeric binding proteins and histone acetyltransferase
factors with similar results in HeLa cells. Nevertheless, larger studies should confirm our findings.},
organization = {European Commission	E17013NK},
organization = {Institut National de la Sante et de la Recherche Medicale (Inserm)
European Commission},
organization = {National Natural Science Foundation of China (NSFC)	31801061},
publisher = {BMC},
keywords = {Human blood},
keywords = {DNA methylation},
keywords = {H3K4me3},
keywords = {Telomere},
keywords = {ChIP-seq},
keywords = {Bisphenol A},
title = {Genome‑wide distribution of histone trimethylation reveals a global impact of bisphenol A on telomeric binding proteins and histone acetyltransferase factors: a pilot study with human and in vitro data},
doi = {10.1186/s13148-022-01408-2},
author = {D'Cruz, Shereen Cynthia and Mustieles Miralles, Vicente and Freire, Carmen and Olivas Martínez, Alicia and Rodríguez Carrillo, Andrea and Fernández Cabrera, Mariana Fátima},
}