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Frontiers in Genomics: Serge McGraw
Embryonic Stem Cells Rely on Sustained DNA Methyltransferase 1 (DNMT1) Activity for Epigenetic Stability and Functional Integrity

24 octubre, 2023 @ 10:00 am

Abstract:
DNA methyltransferase 1 (DNMT1) is critical during early development. Absence of DNMT1 is embryonic lethal and insufficient DNMT1 activity can lead to disorganized cell differentiation, increased cell death of specialized cells and implantation failure. DNMT1 is known for catalyzing DNA methylation maintenance, notably at imprinting control regions (ICR). However, evidence supports DNMT1 functionality beyond and independent of its catalytic role, mainly throughinteraction with histone-modifying enzymes. The scope of its mechanisms is misunderstood, understudied and likely underestimated. To decipher how DNMT1 may be involved in multiple layers of epigenetic regulation, we used transgenic mouse embryonic stem cells (mESC) in which Dnmt1 expression can be robustly controlled (TET-off system). We measured DNA methylation, histone modifications (H3K4me3, H3K27ac, H3K4me1, H3K27me3, H3K9me3) and transcription throughout Dnmt1 inactivation and rescue, and assessed the impact on mESC functions, namely self-renewal and differentiation. We show that interruption of Dnmt1 expression in mESCs induces multi-layered epigenetic instability, reduces self-renewal and disrupts differentiation towards early germ layer cells (endoderm, mesoderm, ectoderm).
Overall, our work further clarifies DNMT1-dependant mechanisms, emphasizing their diversity and importance, and could help understand how early epigenetic perturbations trigger the onset of developmental and complex diseases.

Serge McGraw. CHU Sainte-Justine Research Centre. Université de Montréal

https://research.chusj.org/en/Axes-de-recherche/Bio?id=4d71665a-2f6a-414b-b37d-7c82e09fa27c

https://www.rqr.umontreal.ca/en/team-members/serge-mcgraw-phd-2/

Frontiers in Genomics

Detalles

Fecha:
24 octubre, 2023
Hora:
10:00 am
Categorías del Evento:
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Página Web:
https://www.lcg.unam.mx/transmision-en-vivo

Lugar

Transmisión en vivo
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Organizador

Licenciatura en Ciencias Genómicas