Dynamic changes in the localization of five members of the methyl binding domain (MBD) gene family during murine and bovine preimplantation embryo development

Abstract

There are five methyl binding domain (MBD) proteins characterized by a methyl CpG‐binding domain. Four MBD proteins (MeCP2 and MBDs 1–3) are linked to transcriptional repression and one (MBD4), to DNA repair. During preimplantation development, the embryo undergoes global demethylation following fertilization and selective remethylation following the maternal to zygotic transition (MZT). This study characterized changes in MBD mRNA expression and protein localization during both murine and bovine preimplantation development. These species were selected because they undergo MZT at different developmental stages. Gene expression profiling during preimplantation development detected the presence of all MBDs examined, although stage and species‐specific differences were observed. MBD2 was not expressed in murine or bovine oocytes and MeCP2 was not detected in murine blastocysts, subcellular protein localization was found to vary at time points critical in development. Most MBDs showed species‐specificity in localization patterns and differences were found between individual MBDs. MBD1 localization is consistent with a novel role during MZT for both species. MBD3, known to play a crucial role in murine embryogenesis, was highly localized to the nucleus before and after, but not during the MZT in the bovine. MBD2, MBD4, and MeCP2 show varying patterns of localization which indicate possible roles in the early cleavage stages and in inner cell mass differentiation. Further experiments are currently underway to define discreet functional roles for specific MBDs during bovine preimplantation embryogenesis. Mol. Reprod. Dev. 75: 48–59, 2008. © 2007 Wiley‐Liss, Inc.

Methylation dynamics during folliculogenesis and early embryo development in sheep

“…During embryogenesis, MBD proteins have been implicated in both global transcriptional regulation (Klose & Bird 2006) and more specifically in the repression of Oct4, a pluripotency marker essential for early stages of mammalian embryogenesis (Gu et al 2009). MBD1, 3 and 4 were also shown to be expressed in mouse and bovine oocytes (Ruddock-D'Cruz et al 2008).…”

UCA1, a non‐protein‐coding RNA up‐regulated in bladder carcinoma and embryo, influencing cell growth and promoting invasion

“…The changes of expression of the several representative genes were confirmed through real time PCR (Fig. 4C3-C5), the up-regulated genes including wingless-type MMTV integration site family, member 6 (WNT6) [15], CYP1A1 (cytochrome P450, 1A1) [16], and AURKC (a urora kinase C) [17], and the down-regulated genes including methyl-CpG binding domain protein 3 (MBD3) [18][19][20], and SR (serine/arginine-rich) protein-specific kinase 1 (SRPK1) [21,22], which were identical with the microarray results (Tables 2 and 3). Results represented the mean of three independent experiments performed in triplicates.…”

Epigenetic reprogramming: is deamination key to active DNA demethylation?

“…If DNA demethylation was to be initiated by deaminases and resultant mismatches processed by DNA repair pathways, then the enzymes from this pathways should also be expressed at times when DNA demethylation occurs. Indeed, it has been reported that Mbd4 together with other components of the BER pathway, including APE1, Polβ and DNA ligase 3 are expressed at all stages of mouse preimplantation development (Ruddock-D’Cruz et al 2008, May et al 2009). Moreover, BER enzymes are present in the paternal pronucleus in the zygote and in PGCs at the time of global DNA demethylation (Hajkova et al 2010).…”