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Characteristics of chromatin modifiers and mutant ES cells |
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| Name |
Protein function |
ES cell lines |
Phenotype of KO/DKO mice |
Phenotype of KO/DKO ES cells |
Reference |
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| 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] |
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miRNA, microRNA. | |||||
Jørgensen et al. Genome Biology 2007 8:R169 doi:10.1186/gb-2007-8-8-r169 |
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