PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos

Abstract

The modification of DNA by 5-methylcytosine (5mC) has essential roles in cell differentiation and development through epigenetic gene regulation. 5mC can be converted to another modified base, 5-hydroxymethylcytosine (5hmC), by the tet methylcytosine dioxygenase (Tet) family of enzymes. Notably, the balance between 5hmC and 5mC in the genome is linked with cell-differentiation processes such as pluripotency and lineage commitment. We have previously reported that the maternal factor PGC7 (also known as Dppa3, Stella) is required for the maintenance of DNA methylation in early embryogenesis, and protects 5mC from conversion to 5hmC in the maternal genome. Here we show that PGC7 protects 5mC from Tet3-mediated conversion to 5hmC by binding to maternal chromatin containing dimethylated histone H3 lysine 9 (H3K9me2) in mice. In addition, imprinted loci that are marked with H3K9me2 in mature sperm are protected by PGC7 binding in early embryogenesis. This type of regulatory mechanism could be involved in DNA modifications in somatic cells as well as in early embryos.

Epigenetics and developmental programming of welfare and production traits in farm animals

“…However, the global DNA demethylation observed in the preimplantation embryo excludes certain regions of the genome. Indeed, imprinted genes are protected from this DNA demethylation activity, and recent evidence shows that the maternal and paternal imprints are protected by different mechanisms (Nakamura et al 2012). The extensive demethylation between the zygote and the morula stage prepares the chromatin of the totipotent blastomeres for the segregation of the lineages that will contribute to the formation of the conceptus.…”

Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

“…ChIP-seq Spermatozoa chromatin was prepared as described previously, 61 with slight modifications. Briefly, spermatozoa were washed in PBS and suspended in lysis buffer (0.1% SDS, 0.5% Triton X-100 in PBS) for 20 min on ice to eliminate white blood cell contamination.…”

Efectos de los RNAm maternos sobre la maduración del ovocito y el desarrollo embrionario temprano en mamíferos

“…Al mismo tiempo, a diferencia del genoma paterno, en el genoma materno la desmetilación sucede de forma paulatina a través de varios ciclos de división celular (92) . Esto es debido a que la proteína materna STELLA, también conocida como PGC7, protege al DNA de la desmetilación, impidiendo la oxidación de 5mC a 5hmC (93) . specifically the female pronucleus presents a global loss of methylation, which by immunofluorescence assay has been associated with the enzyme TET3 present in this pronucleus, what is not seen in normal embryos (69,93) .…”

“…At the same time, unlike the parental genome, in the maternal genome demethylation occurs gradually through several cycles of cell division (92) . This is due to the fact that the maternal protein STELLA, also known as PGC7, protects the DNA demethylation, preventing the oxidation of 5cM to 5hmC (93) . STELLA is present in the primordial germ cells and their function is required for embryonic development (94,95) , binds to the protein 5 union Ran and is transported to the nucleus, where it joined the lysine 9 of histone 3 in maternal chromatin, which reduces the union of the enzyme TET3, implying 5mC sites without oxidation (92,96) .…”

“…Esto es debido a que la proteína materna STELLA, también conocida como PGC7, protege al DNA de la desmetilación, impidiendo la oxidación de 5mC a 5hmC (93) . specifically the female pronucleus presents a global loss of methylation, which by immunofluorescence assay has been associated with the enzyme TET3 present in this pronucleus, what is not seen in normal embryos (69,93) . Going from zygote to 2-cells embryo, most of the male genome is demethylated and only persist the ICRs methylated of mono-allelic expression, in the case of the maternal genome ICRs regions are methylated due to the protection provided by STELLA; however in the paternal genome given the speed that occurs in the process of demethylation, keeping the ICRs regions methylated is a problem, which is solved thanks to the action of the maternal protein TRIM28 (97) .…”