Table 6.
Description of candidate CHD-related MEGs
| Gene symbol (mouse/human) | Gene name | Impact/function of maternal gene in mouse models | Human phenotype |
|---|---|---|---|
| Bcas2/BCAS2 | BCAS2 pre-mRNA processing factor | developmental arrest at two- to four-cell stage; compromised DNA damage response in early embryos; accumulation of DNA damage and micronuclei28 | |
| Cdc20/CDC20 | cell division cycle 20 | needed for first mitotic division29 | EEA, FF, OMA30 |
| Cdx2/CDX2 | caudal type homeobox 2 | 55% of embryos from maternal knockouts arrest at morula stage; 69% of embryos from maternal-zygotic knockouts arrest at morula stage; associated with cell death and specification of the trophectoderm31 | |
| Ctcf/CTCF | CCCTC-binding factor | increased zygotic lethality and increased methylation of the H19 differentially methylated domain32; increased meiotic and mitotic errors, differential zygotic gene expression, and apoptosis33 | |
| Dnmt3a/DNMT3A | DNA methyltransferase 3 alpha; | hypomethylation and aberrant expression of maternally imprinted genes in the embryo34; embryonic death before E11.5 with pericardial edema, lack of brachial arches, and open neural tube defects.34,35 | |
| Ezh2/EZH2 | enhancer of zeste 2 polycomb repressive complex 2 subunit | severe growth retardation in neonates14; required for establishment of H3K27me3 in zygotes36 | |
| Igf2bp2/IGF2BP2 | insulin-like growth factor 2 mRNA binding protein 2 | subfertilility; 94% of embryos die prior to blastocyst stage; downregulation of transcription during zygotic genome activation37 | |
| Kdm4a/KDM4A | lysine demethylase 4a | majority of embryos fail to develop past the two- to four-cell stage; mediates H3K9me3 demethylation at broad domains of H3K4me3 in oocytes; associated with decreased expression of genes linked to zygotic genome activation38,39 | |
| Khdc3/KHDC3L | KH domain containing 3 like | delays pre-implantation development; high incidence of aneuploidy; inactivation of spindle assembly checkpoint40; member of the subcortical maternal complex in mouse and human41 | EEA, HM, RPL42, 43, 44; DNA methylation loss and imprinting defects45 |
| Kmt2d/KMT2D | lysine methyltransferase 2D | majority of embryos arrest at one- to two-cell stage; controls promoter-specific chromatin modification during oogenesis and early development46 | |
| Pum1/PUM1 | Pumilio RNA binding family member 1 | abnormal pre-implantation development; regulation of maternal mRNA47 | |
| Rnf2/RNF2 | ring finger protein 2 | double-maternal knockout of Rnf2 and Ring2 (components of polycomb repressive complex 1) results in embryonic arrest at 2-cell stage and impaired zygotic genome activation48 | |
| SMARCA4 | SWI/SNF-related, matrix-associated, actin dependent regulator of chromatin, subfamily A, member 4 | embryonic arrest at two-cell stage; impaired zygotic genome activation49 | |
| Trip13/TRIP13 | thyroid hormone receptor interactor 13 | oocyte loss; defect in double-strand break repair | OMA, ZCF50 |
EEA, early embryonic arrest; FF, fertilization failure; HM, hydatidiform mole; IF, implantation failure; OMA, oocyte maturation arrest.
Description of genes in Table 5.