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Histone deacetylase 1 (HDAC 1) knockout mouse embryonic stem cell line

Invented by Shaun Cowley
Invented at University Of Leicester

Info

Catalogue Number 158383
Antigen/Gene or Protein Targets Histone deacetylase 1
Parental Line E14 ES cell line expressing an inducible Cre/Estrogen Receptor (CreER) construct from the endogenous ROSA26 locus
Synonyms RPD3L1
Tissue Embryo
Disease Keywords embryo lethality
Model Knock-Out
Relevance Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Histone deacetylases (HDAC) 1 and 2 are highly similar enzymes that help regulate chromatin structure as the core catalytic components of corepressor complexes. Although tissue-specific deletion of HDAC1 and HDAC2 has demonstrated functional redundancy, germ-line deletion of HDAC1 in the mouse causes early embryonic lethality, whereas HDAC2 does not.
Production Details E14 ES cells, expressing a CreER fusion protein from the ROSA26 locus, were used to generate HDAC1Lox/Lox; CreER and HDAC2Lox/Lox; CreER cell lines by consecutive rounds of gene targeting.
Conditional Yes
Conditional Description Induction of Cre activity by addition of 4-hydroxy tamoxifen (OHT) to the growth media resulted in complete recombination of each allele and deletion of exon 2 (HDAC1Δ2/Δ2 or HDAC2 Δ2/Δ2) within 24 h
Research Area Developmental Biology, Reproductive Biology
Notes Loss of exon 2 via the conditional KO disrupts the ORF of both HDAC1 and HDAC2 such that a premature stop codon is introduced in exon 3. Following this deletion of exon 2 a further 4–5 days of culture are required before HDAC1 and HDAC2 protein levels are reduced below 10% of those of control cells.
Loss of HDAC1 results in decreased deacetylase activity associated with HDAC1/2 complexes and an increase H3K56Ac.

References

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References: 1 entry

Dovey et al. 2010. Proc Natl Acad Sci U S A. 107(18):8242-7. PMID: 20404188.


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References: 1 entry

Dovey et al. 2010. Proc Natl Acad Sci U S A. 107(18):8242-7. PMID: 20404188.


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