From: The impact of chromatin modifiers on the timing of locus replication in mouse embryonic stem cells
Name | Protein function | ES cell lines | Phenotype of KO/DKO mice | Phenotype of KO/DKO ES cells | Reference |
---|---|---|---|---|---|
Mll | HMTase: tri-methylation of H3K4 | KO: High 6 | Embryonic lethal (E11.5-14.5) Homeotic transformations Mis-regulation of Hox gene expression | Mis-regultion of Hox genes Failure of in vitro differentiation to hematopoietic pre-cursors | [42-44] |
Eed | Subunit of PRC2 Cofactor for Ezh2 (H3K27 HMTase) | KO: B1.3, G8.1 | Embryonic lethal (E6.5) Failure to maintain inactive X in trophoblast derivatives | Loss of H3K27me2/3 Reduced H3K27me1 Contribute to all tissues of chimeras | [4,45-47] |
Dnmt1 | Maintenance DNA methyl transferase | KO: c/c | Embryonic lethal (E11.5) | Reduced DNA methylation level Reduced differentiation | [36,48,49] |
Dnmt 3a/3b | De novo DNA methyl transferase | DKO: clone 10 (early passage) | Embryonic lethal (E11.5) | Lack de novo DNA methylation activity DNA methylation levels slightly reduced in early passage (severly reduced in late passage cells) Retains differentiation potential at early passages | [27,37,50] |
Mbd3 | Subunit of NuRD (nucleosome remodeling and HDAC complex) | KO: Fix2 | Embryonic lethal (implantation) | Loss of the NuRD (nucleosome remodeling and HDAC) complex Severe differentiation block | [38,51] |
G9a | HMTase: H3K9me H3K9me2 euchromatic | WT: Col4 KO: 2-3 Tg: 15-3 | Embryonic lethal (E12.5) | Reduced H3K9me2 Increased H3K4me2, H3K9ac Reduced H3K9 methylation in euchromatin | [18,25] |
Suv39 h1/h2 | H3K9me3 (hetero-chromatic) | WT: wt26 DKO: DN57, DN72 | Increased prenatal lethality Growth retarded B-cell lymphomas Male sterility Chromosome instablility in fibroblasts | Reduced H3K9me3 level; Reduced H3K9me3 at pericentric heterochromatin Increased H3K27me3 at pericentric heterochromatin Decreased CpG methylation of satellite repeats Increased transcription of major/minor satellite | [25,35,52,53] |
Dicer | RNase, essential for siRNA/miRNA pathway in mammals | WT: D3 KO: D3-S5, D3-S6 | Embryonic lethal (E7.5) | Increased transcription of repeats Slow growth | [30,54,55] |