BIOMAT Database Logo BIOMAT Database Logo

Reduced histone biotinylation in multiple carboxylase deficiency patients: a nuclear role for holocarboxylase synthetase. 2004

Monica A Narang, and Richard Dumas, and Linda M Ayer, and Roy A Gravel
Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.

The attachment of biotin to apocarboxylases is catalyzed by holocarboxylase synthetase (HCS). An inherited deficiency of HCS results in the disorder 'multiple carboxylase deficiency', which is characterized by reduced activity of all biotin-dependent carboxylases. Here we show that the majority of HCS localizes to the nucleus rather than the cytoplasm based on immunofluorescence studies with antibodies to peptides and full length HCS and on the expression of recombinant HCS. Subnuclear fractionations indicate that HCS is associated with chromatin and the nuclear lamina, the latter in a discontinuous distribution in high salt-extracted nuclear membranes. During mitosis, HCS resolves into ring-like particles which co-localize with lamin B. Nuclear HCS retains its biotinylating activity and was shown to biotinylate purified histones in vitro. Significantly, fibroblasts from patients with HCS deficiency are severely deficient in histone biotinylation in addition to the deficiency of carboxylase activities. We propose that the role of HCS in histone modification may be linked to the participation of biotin in the regulation of gene expression or cell division and that affected patients may have additional disease beyond that due to the effect on carboxylases.

UI MeSH Term Description Entries
D009100 Multiple Carboxylase Deficiency A deficiency in the activities of biotin-dependent enzymes (propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, and PYRUVATE CARBOXYLASE) due to one of two defects in BIOTIN metabolism. The neonatal form is due to HOLOCARBOXYLASE SYNTHETASE DEFICIENCY. The late-onset form is due to BIOTINIDASE DEFICIENCY. Carboxylase Deficiency, Multiple,Combined Carboxylase Deficiency,Carboxylase Deficiency, Combined,Deficiency, Combined Carboxylase,Deficiency, Multiple Carboxylase,Carboxylase Deficiencies, Combined,Carboxylase Deficiencies, Multiple,Combined Carboxylase Deficiencies,Deficiencies, Combined Carboxylase,Deficiencies, Multiple Carboxylase,Multiple Carboxylase Deficiencies
D010957 Plasmids Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS. Episomes,Episome,Plasmid
D011233 Precipitin Tests Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate. Precipitin Test,Test, Precipitin,Tests, Precipitin
D002467 Cell Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D002843 Chromatin The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell. Chromatins
D005455 Fluorescent Antibody Technique Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy. Antinuclear Antibody Test, Fluorescent,Coon's Technique,Fluorescent Antinuclear Antibody Test,Fluorescent Protein Tracing,Immunofluorescence Technique,Coon's Technic,Fluorescent Antibody Technic,Immunofluorescence,Immunofluorescence Technic,Antibody Technic, Fluorescent,Antibody Technics, Fluorescent,Antibody Technique, Fluorescent,Antibody Techniques, Fluorescent,Coon Technic,Coon Technique,Coons Technic,Coons Technique,Fluorescent Antibody Technics,Fluorescent Antibody Techniques,Fluorescent Protein Tracings,Immunofluorescence Technics,Immunofluorescence Techniques,Protein Tracing, Fluorescent,Protein Tracings, Fluorescent,Technic, Coon's,Technic, Fluorescent Antibody,Technic, Immunofluorescence,Technics, Fluorescent Antibody,Technics, Immunofluorescence,Technique, Coon's,Technique, Fluorescent Antibody,Technique, Immunofluorescence,Techniques, Fluorescent Antibody,Techniques, Immunofluorescence,Tracing, Fluorescent Protein,Tracings, Fluorescent Protein
D006657 Histones Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. Histone,Histone H1,Histone H1(s),Histone H2a,Histone H2b,Histone H3,Histone H3.3,Histone H4,Histone H5,Histone H7
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000906 Antibodies Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured

Related Publications

Monica A Narang, and Richard Dumas, and Linda M Ayer, and Roy A Gravel
[Holocarboxylase synthetase deficiency (early-onset multiple carboxylase deficiency)].
January 1998, Ryoikibetsu shokogun shirizu,
Monica A Narang, and Richard Dumas, and Linda M Ayer, and Roy A Gravel
Reduced half-life of holocarboxylase synthetase from patients with severe multiple carboxylase deficiency.
June 2008, Human mutation,
Monica A Narang, and Richard Dumas, and Linda M Ayer, and Roy A Gravel
Heterogeneity of holocarboxylase synthetase in patients with biotin-responsive multiple carboxylase deficiency.
March 1985, American journal of human genetics,
Monica A Narang, and Richard Dumas, and Linda M Ayer, and Roy A Gravel
A novel, enigmatic histone modification: biotinylation of histones by holocarboxylase synthetase.
December 2008, Nutrition reviews,
Monica A Narang, and Richard Dumas, and Linda M Ayer, and Roy A Gravel
Impaired biotinidase activity disrupts holocarboxylase synthetase expression in late onset multiple carboxylase deficiency.
December 2008, The Journal of biological chemistry,
Monica A Narang, and Richard Dumas, and Linda M Ayer, and Roy A Gravel
Mutant holocarboxylase synthetase: evidence for the enzyme defect in early infantile biotin-responsive multiple carboxylase deficiency.
December 1981, The Journal of clinical investigation,
Monica A Narang, and Richard Dumas, and Linda M Ayer, and Roy A Gravel
[Delayed onset holocarboxylase synthetase deficiency with normal pyruvate carboxylase activity].
March 2014, Anales de pediatria (Barcelona, Spain : 2003),
Monica A Narang, and Richard Dumas, and Linda M Ayer, and Roy A Gravel
[Holocarboxylase synthetase deficiency].
January 2001, Ryoikibetsu shokogun shirizu,
Monica A Narang, and Richard Dumas, and Linda M Ayer, and Roy A Gravel
Holocarboxylase synthetase interacts physically with euchromatic histone-lysine N-methyltransferase, linking histone biotinylation with methylation events.
August 2013, The Journal of nutritional biochemistry,
Monica A Narang, and Richard Dumas, and Linda M Ayer, and Roy A Gravel
Lactic acidosis in biotin-responsive multiple carboxylase deficiency caused by holocarboxylase synthetase deficiency of early and late onset.
October 1982, The Journal of pediatrics,
Copied contents to your clipboard!