TABLE 1.
| Gene | Biochemical Function | ES Cell Phenotype | Mouse Phenotype |
|---|---|---|---|
| Hdac1/2 | Deacetylation of lysine residues on histone tails and other proteins | Hdac1−/− ES cells are viable with decreased proliferation and colony formation [102]. Hdac2−/− ES cells are viable and show no defect in proliferation or differentiation [103]. | Hdac1−/− embryos die between E9.5 and E10.5. Hdac2−/− embryos exhibit perinatal lethality due to cardiac defects [104]. Conditional deletion of Hdac1/2 indicates that these genes are redundantly required in a broad range of organs (e.g. neurons, T cells, adipocytes, kidneys) [103-105]. |
| Chd3/4/5 | Helicase/ATPase that uses the energy from ATP to remodel chromatin through histone sliding; PHD domains bind histone H3 [81] | None reported1 | Chd4 conditional mutants revealed it is required for T cell, hematopoetic stem cell, epidermal progenitor cell, and renal progenitor cell self-renewal and differentiation [19, 45, 60]. |
| Mbd2/3 | Methyl-CpG binding domain; Mbd2, but not Mbd3, binds methlylated DNA with high affinity [21] | Mbd3−/− ES cells are viable but fail to downregulate progenitor genes, and fail to differentiate [50]. | Mbd2−/− embryos are viable and fertile but the mothers have a nurturing defect. Mbd3−/− embryos are embryonic lethal between E3.5 and E8.5 [43]. |
| Mta1/2/3 | SANT and GATA DNA binding domains; directly interacts with HDAC proteins and Rbbp4/7 [41, 106] | None reported | Mta1−/− embryos are viable and exhibit cardiovascular, craniofacial, integument and skeletal defects [107] [MGI, 2010]2. Mta2−/− mutants exhibit skin lesions, bodyweight loss, glomerulonephritis, liver inflammation, and production of autoantibodies [108]. |
| Rbbp4/7 | Histone H4 binding; associates with multiple cellular proteins and thought to act as a scaffold; interacts directly with MTA1 [106] | None reported | Conditional Rbbp7 mutants have decreased CD8-positive T cell numbers, and male embryos of a gene trap allele have abnormal developmental patterning [MGI 2008, 2010]3. |
| Gata2a/2b | Nuclear zinc finger protein that binds DNA and directly interacts with Mbd2/3 [27] | None reported | Gata2a−/− embryos display anemia by E10.5, yolk sacs are devoid of red blood cells, and are embryonic lethal by E11.5 [109]. |
1
Databases searched for ES cell phenotype and mouse phenotype included PubMed (www.ncbi.nlm.nih.gov/pubmed), Mouse Genome Informatics (MGI, www.informatics.jax.org), and Gene Cards (www.genecards.org).
2
Wellcome Trust Sanger Institute, Alleles produced for the EUCOMM and EUCOMMTools projects by the Wellcome Trust Sanger Institute. MGI Direct Data Submission. 2010.
3
Mouse Genome Informatics (MGI) and National Center for Biotechnology Information (NCBI), Mouse Gene Trap Data Load from dbGSS. Database Download. 2008, and Wellcome Trust Sanger Institute, Alleles produced for the EUCOMM and EUCOMMTools projects by the Wellcome Trust Sanger Institute. MGI Direct Data Submission. 2010.