Uptake, Localization, and Noncarboxylase Roles of Biotin

Zempleni, Janos

doi:10.1146/annurev.nutr.25.121304.131724

Cited by 168 publications

(123 citation statements)

References 144 publications

(196 reference statements)

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“…However, it remains uncertain how the same enzyme may act as a biotinyl transferase in one case and as a debiotinylase in another. It has been proposed that regulation of biotinidase is achieved by interactions with chromatin-associated proteins, posttranslational modifications and alternative splicing, and substrate availability [17]. Note that we have detected biotinidase in human cell nuclei [11], whereas other groups suggest that biotinidase is primarily an extranuclear protein [23].…”

Section: Introductioncontrasting

confidence: 50%

“…Evidence that biotinylation of histones plays a role in cell proliferation [10], cellular response to DNA damage [15], mitotic condensation of chromatin [16] and heterochromatin structures and gene silencing has been provided (Camporeale et al, submitted for publication). Collectively, the binding of biotin to histones participates in epigenetic events that are crucial for maintaining genomic stability and chromatin structure [17].…”

Section: Introductionmentioning

confidence: 99%

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An avidin-based assay for histone debiotinylase activity in human cell nuclei

Chew

Sarath

Zempleni

2007

The Journal of Nutritional Biochemistry

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The covalent binding of biotin to histones participates in heterochromatin formation, cell cycle progression and cellular response to DNA breaks. Biotinylation of histones appears to be a reversible process, but the identity of enzymes that remove biotin marks is largely unknown. Our long-term goal is to identify histone debiotinylases in human cells. Here we developed an avidin-based plate assay to quantify histone debiotinylase activities in nuclear extracts. This assay is an essential first step in purifying and identifying histone debiotinylases from human cells. Using this assay, we demonstrated that debiotinylation of histones depends on temperature and pH, consistent with enzyme catalysis. Experiments with purified histones, proteases and protease inhibitors provide evidence that removal of biotin marks from histones is mediated by debiotinylases rather than by proteases. Activities of histone debiotinylases varied among human tissues: colon = lung N placenta = liver N lymphoid cells. This assay proved useful in monitoring activities of putative histone debiotinylases during their partial purification from cells. Collectively, this assay is a useful tool for investigating histone debiotinylases in human tissues. D

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Section: Introductioncontrasting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

An avidin-based assay for histone debiotinylase activity in human cell nuclei

Chew

Sarath

Zempleni

2007

The Journal of Nutritional Biochemistry

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“…Recent studies suggest additional roles for this vitamin in cell signaling, gene expression, and chromatin structure in mammalian cells (reviewed in ref. 1). Biotin is synthesized by many bacteria, certain archaea, fungi, and plants (reviewed in ref.…”

Section: B Iotin (Vitamin H) Is An Essential Cofactor In Carboxylationmentioning

confidence: 99%

Biotin uptake in prokaryotes by solute transporters with an optional ATP-binding cassette-containing module

Hebbeln

Rodionov

Alfandega

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

132

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BioMNY proteins are considered to constitute tripartite biotin transporters in prokaryotes. Recent comparative genomic and experimental analyses pointed to the similarity of BioMN to homologous modules of prokaryotic transporters mediating uptake of metals, amino acids, and vitamins. These systems resemble ATP-binding cassette-containing transporters and include typical ATPases (e.g., BioM). Absence of extracytoplasmic solute-binding proteins among the members of this group, however, is a distinctive feature. Genome context analyses uncovered that only onethird of the widespread bioY genes are linked to bioMN. Many bioY genes are located at loci encoding biotin biosynthesis, and others are unlinked to biotin metabolic or transport genes. Heterologous expression of the bioMNY operon and of the single bioY of the ␣-proteobacterium Rhodobacter capsulatus conferred biotin-transport activity on recombinant Escherichia coli cells. Kinetic analyses identified BioY as a high-capacity transporter that was converted into a high-affinity system in the presence of BioMN. BioMNY- Biotin is synthesized by many bacteria, certain archaea, fungi, and plants (reviewed in ref. 2). Several metabolic routes seem to exist for the synthesis of the intermediate pimeloyl-CoA, which then is converted into biotin in a four-step path encoded by the universal genes bioF, bioA, bioD, and bioB (3, 4). In plants, the pathway is distributed between the cytosol and the mitochondria. At least the final step, catalyzed by biotin synthase, occurs in mitochondria. This enzyme, a member of the radical SAM enzyme family, inserts a sulfur atom into dethiobiotin in a complex reaction that is linked to mitochondrial iron/sulfur metabolism (2).Biotin uptake has been analyzed in eukaryotes. In mammalian cells, the vitamin is transported across the plasma membrane by a sodium-dependent multivitamin transporter and, at least in certain tissues, by monocarboxylate transporter 1 (1). In the naturally biotin-auxotrophic yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, biotin uptake is mediated by unrelated proton symporters (5). Surprisingly little is known on the mechanisms behind biotin transport into prokaryotic cells, and multiple systems seem to exist. Active transport was observed for Escherichia coli K-12 Ͼ30 years ago (6). Despite extensive experimental work, knowledge of the complete genome sequence, and assignment of the biotin-transport locus to the 75-min genomic region, the gene(s) for the biotin transporter has not yet been identified. Recent studies by Walker and Altman (7) suggest that this system in E. coli and related Gram-negative bacteria not only transports the small vitamin, but in addition facilitates the uptake of biotinylated peptides with chain lengths up to 31 amino acid residues.In 2002, Entcheva et al. (8) reported that mutations in bioM and bioN lead to reduced biotin uptake in Sinorhizobium meliloti. Because the products of these two genes share distinct similarity with CbiO and CbiQ, which are components of prokary...

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“…26 The detection of HCS in cell nuclei and the HCS-catalyzed biotinylation of histones in vitro suggested that HCS might be responsible for biotin attachment to histones in vivo. 20 However, the recent finding of Streaker and Beckett 19 that the bio-5 0 -AMP product of BirA was sufficient, in the absence of enzyme, to produce biotin transfer to BCCP87 led us to examine the behavior of HCS and BirA toward histones, that is, whether the rate and specificity of biotin addition to histones depended on the BPL or whether the role of the biotin ligase might be limited to the generation of bio-5 0 -AMP.…”

Section: Discussionmentioning

confidence: 99%

Nonenzymatic biotinylation of histone H2A

et al. 2009

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Holocarboxylase synthetase (HCS, eukaryotic enzyme) and BirA (prokaryotic) are biotin protein ligases that catalyze the ATP-dependent attachment of biotin to apocarboxylases via the reactive intermediate, bio-5 0 -AMP. In this study, we examined the in vitro mechanism of biotin attachment to histone H2A in the presence of HCS and BirA. The experiment derives from our observations that HCS is found in the nucleus of cells in addition to the cytoplasm, and it has the ability to attach biotin to histones in vitro (Narang et al., Hum Mol Genet 2004; 13:15-23). Using recombinant HCS or BirA, the rate of biotin attachment was considerably slower with histone H2A than with the biotin binding domain of an apocarboxylase. However, on incubation of recombinant H2A with chemically synthesized bio-5 0 -AMP, H2A was observed to be rapidly labeled with biotin in the absence of enzyme. Nonenzymatic biotinylation of a truncated apocarboxylase (BCCP87) has been previously reported (Streaker and Beckett, Protein Sci 2006; 15:1928-1935), though at a much slower rate than we observe for H2A. The specific attachment sites of nonenzymatically biotinylated recombinant H2A at different time points were identified using mass spectrometry, and were found to consist of a similar pattern of biotin attachment as seen in the presence of HCS, with preference for lysines in the highly basic N-terminal region of the histone. None of the lysine sites within H2A resembles the biotin attachment consensus sequence seen in carboxylases, suggesting a novel mechanism for histone biotinylation.

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Uptake, Localization, and Noncarboxylase Roles of Biotin

Cited by 168 publications

References 144 publications

An avidin-based assay for histone debiotinylase activity in human cell nuclei

An avidin-based assay for histone debiotinylase activity in human cell nuclei

Biotin uptake in prokaryotes by solute transporters with an optional ATP-binding cassette-containing module

Nonenzymatic biotinylation of histone H2A

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