Table 1

Characteristics of chromatin modifiers and mutant ES 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]


miRNA, microRNA.

Jørgensen et al. Genome Biology 2007 8:R169   doi:10.1186/gb-2007-8-8-r169

Open Data