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. 2024;16(18):1253-1264.
doi: 10.1080/17501911.2024.2397329. Epub 2024 Sep 19.

Impact of prematurity on LINE-1 promoter methylation

Paulo Victor Barbosa Eleutério Dos Santos  1   2 , Aline de Araújo Brasil  1 , Leo Travassos Vieira Milone  1   3 , Georgia Chalfun  1   4 , Stephanie Cristina Alves de Oliveira Saide  1   3 , Margarida Dos Santos Salú  1 , Mariana Barros Genuíno de Oliveira  1 , Jaqueline Rodrigues Robaina  1 , Fernanda Lima-Setta  1 , Gustavo Rodrigues-Santos  1 , Maria Clara de Magalhães-Barbosa  1 , Antônio José Ledo Alves da Cunha  1   2 , Arnaldo Prata-Barbosa  1   2
Affiliations

Impact of prematurity on LINE-1 promoter methylation

Paulo Victor Barbosa Eleutério Dos Santos et al. Epigenomics. 2024.

Abstract

Aim: Promoter methylation of LINE-1 may be affected by prematurity, but there is little evidence in the literature.Materials & methods: Blood from premature and full-term neonates on days 0, 5, 30 and 90 was analyzed for DNA methylation percentage in a promoter region of the LINE-1, after bisulfite conversion and pyrosequencing.Results: Premature infants, as a whole, showed significantly lower methylation percentage at birth, but this difference diminished over time. However, the subgroup of extremely premature (<28 weeks gestational age) had higher methylation percentages, similar to full-term newborns.Conclusion: This research underscores the critical role of prematurity on the methylation pattern of LINE-1. These findings underline the complexity of epigenetic regulation in prematurity and emphasize the need for further studies.

Keywords: DNA methylation; LINE-1; epigenetics; newborn; prematurity; retroelements.

Plain language summary

Premature birth can have significant effects on a baby's development and long-term health. This study investigates how being born prematurely affects a process called DNA methylation, which can influence how genes are turned on or off. Specifically, we examined the LINE-1 promoter, a frequently occurring region of DNA known for its role in regulating gene activity.We collected blood samples from both premature and full-term newborns at birth and at several points in the early months of life. Our findings showed that premature babies have lower levels of LINE-1 promoter methylation at birth compared with full-term babies. These differences in methylation could possibly affect the babies' development and health as they grow.Our research highlights the need for continued study in this area to explore how these epigenetic changes impact long-term health and to develop strategies to mitigate these effects.

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Conflict of interest statement

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.
Distribution of global methylation percentage in full-term and preterm newborns. At birth (A), significantly higher methylation percentages were observed in the full-term newborn group. This percentage was still higher on the fifth day of life (B), but the difference between the groups did not show statistical significance, although with a marginal p-value.
Figure 2.
Figure 2.
Distribution of global methylation percentage in term newborns, very preterm (28 to less than 32 weeks gestational age), and extremely preterm infants (less than 28 weeks gestational age) at birth (A), on the fifth day of life (B), on the thirtieth day of life (C) and the ninetieth day of life (D). In panel A, a significant difference in methylation is observed between full-term and very preterm neonates, which is not observed between very preterm and extremely preterm. Extremely preterm infants had a methylation percentage closer to full-term newborns than to very preterm ones (not statistically significant). In panel B, the difference in global methylation between full-term and very preterm infants is still statistically significant, although not significant between very preterm and extremely preterm infants, as well as between full-term infants and extremely preterm infants. In panels (C & D), there were no differences in the global methylation percentage between the subgroups of preterm infants, although the p-value on D90 (D) approached statistical significance.
Figure 3.
Figure 3.
Temporal evolution of site-specific methylation in preterm newborns at CpG sites 1 (A), CpG 2 (B), CpG 3 (C) and CpG 4 (D) of the transposable element LINE-1 at time points D0, D5, D30 and D90, showing positive slopes but not significant trends.
Figure 4.
Figure 4.
Temporal evolution of global methylation in LINE-1 CpG sites in preterm newborns at D0, D5, D30 and D90 shows a positive slope but not a significant trend.
See this image and copyright information in PMC

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