Immunological Studies of Families Segregating the Silent Gene for Plasma Cholinesterase

Whíttaker, Mary; Jones, Jeffrey W.; Braven, J.

doi:10.1159/000153982

Cited by 5 publications

(3 citation statements)

References 11 publications

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“…Cell-type specific Brd4 peaks match well with the enrichment of H4ac (Fig, 6 and Additional file 6 : Figure S5), showing the high affinity of Brd4 with H4ac. Brd4 overlapped with more than 20 % of pluripotent factors ( Oct4 , Sox2 , and Nanog ) and more than 30 % of c-Myc and n-Myc binding sites within 1Kbps [ 42 ]. However, the overlap with an insulator CTCF is only 6 percent.…”

Section: Resultsmentioning

confidence: 99%

Histone H4 acetylation and the epigenetic reader Brd4 are critical regulators of pluripotency in embryonic stem cells

et al. 2016

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BackgroundPluripotent cells can be differentiated into many different cell types in vitro. Successful differentiation is guided in large part by epigenetic reprogramming and regulation of critical gene expression patterns. Recent genome-wide studies have identified the distribution of different histone-post-translational modifications (PTMs) in various conditions and during cellular differentiation. However, our understanding of the abundance of histone PTMs and their regulatory mechanisms still remain unknown.ResultsHere, we present a quantitative and comprehensive study of the abundance levels of histone PTMs during the differentiation of mouse embryonic stem cells (ESCs) using mass spectrometry (MS). We observed dynamic changes of histone PTMs including increased H3K9 methylation levels in agreement with previously reported results. More importantly, we found a global decrease of multiply acetylated histone H4 peptides. Brd4 targets acetylated H4 with a strong affinity to multiply modified H4 acetylation sites. We observed that the protein levels of Brd4 decreased upon differentiation together with global histone H4 acetylation. Inhibition of Brd4:histone H4 interaction by the BET domain inhibitor (+)-JQ1 in ESCs results in enhanced differentiation to the endodermal lineage, by disrupting the protein abundance dynamics. Genome-wide ChIP-seq mapping showed that Brd4 and H4 acetylation are co-occupied in the genome, upstream of core pluripotency genes such as Oct4 and Nanog in ESCs and lineage-specific genes in embryoid bodies (EBs).ConclusionsTogether, our data demonstrate the fundamental role of Brd4 in monitoring cell differentiation through its interaction with acetylated histone marks and disruption of Brd4 may cause aberrant differentiation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2414-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Histone H4 acetylation and the epigenetic reader Brd4 are critical regulators of pluripotency in embryonic stem cells

et al. 2016

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“…24 Immunoassays have also been described which can determine enzyme concentration as opposed to activity. 25 Immunoassays, using antibody raised against usual enzyme, have been important in demonstrating the existence of types of`silent' variant, 26 but their use has been mainly con¢ned to the research arena because the clinical value of cholinesterase is associated with its activity rather than its concentration.…”

Section: Measurement Of Enzyme Activitymentioning

confidence: 99%

Cholinesterase: phenotyping and genotyping

Goodall

2004

Ann Clin Biochem

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The plasma enzyme butyrylcholinesterase (BChE) is of clinical interest because of the occurrence of genetic variants with decreased ability to hydrolyse, and therefore inactivate, muscle-relaxant drugs such as suxamethonium. Analysis of BChE involves the determination of both enzyme activity and biochemical phenotypes which are used to determine the risk of so-called 'scoline apnoea'. Problems in analysis arise from both the lack of a universally accepted reference method and the variety of substrates and conditions employed for the determination of activity and phenotypes. Phenotype is determined by the use of speci c enzyme inhibitors that produce phenotype-speci c patterns of 'inhibitor numbers'. DNA analysis is now possible, and true genotypes can be obtained. The nomenclature in use for cholinesterase studies can cause problems in interpretation and reporting as there is poor understanding of the difference between phenotype and genotype, and terms are often, inappropriately, transposed. Techniques for both biochemical and molecular analysis of the enzyme are discussed.

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“…Whittaker et al [98] investigated seven families, all of which had isolated an apparent silent gene homozygote. Using enzyme-linked immunosorbent assays they confirmed that only one of the seven propositi could be truly classified as S/S.…”

Section: Inherited Variationsmentioning

confidence: 99%

Cholinesterase Its significance in anaesthetic practice

1997

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SummaryPlasma cholinesterase is an enzyme which has importance to the anaesthetist primarily for its rôle in the metabolism of suxamethonium, although other anaesthetic related drugs that this enzyme metabolises are also increasingly important. In this article we review current thoughts on the function, profile and chemistry of plasma cholinesterase. Causes of variations in the activity of the enzyme are described and the basis of genetic variations is explained.

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Immunological Studies of Families Segregating the Silent Gene for Plasma Cholinesterase

Cited by 5 publications

References 11 publications

Histone H4 acetylation and the epigenetic reader Brd4 are critical regulators of pluripotency in embryonic stem cells

Histone H4 acetylation and the epigenetic reader Brd4 are critical regulators of pluripotency in embryonic stem cells

Cholinesterase: phenotyping and genotyping

Cholinesterase Its significance in anaesthetic practice

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