Dataset Information

Proof-of-Concept Method to Study Uncharacterized Methyltransferases Using PRDM15.

ABSTRACT: The PRDM family of methyltransferases has been implicated in cellular proliferation and differentiation and is deregulated in human diseases, most notably in cancer. PRDMs are related to the SET domain family of methyltransferases; however, from the 19 PRDMs only a few PRDMs with defined enzymatic activities are known. PRDM15 is an uncharacterized transcriptional regulator, with significant structural disorder and lack of defined small-molecule binding pockets. Many aspects of PRDM15 are yet unknown, including its structure, substrates, reaction mechanism, and its methylation profile. Here, we employ a series of computational approaches for an exploratory investigation of its potential substrates and reaction mechanism. Using the knowledge of PRDM9 and current knowledge of PRDM15 as basis, we tried to identify genuine substrates of PRDM15. We start from histone-based peptides and learn that the native substrates of PRDM15 may be non-histone proteins. In the future, a combination of sequence-based approaches and signature motif analysis may provide new leads. In summary, our results provide new information about the uncharacterized methyltransferase, PRDM15.

SUBMITTER: Zhao LN

PROVIDER: S-EPMC9861158 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Proof-of-Concept Method to Study Uncharacterized Methyltransferases Using PRDM15.

Zhao Li-Na LN Guccione Ernesto E Kaldis Philipp P

International journal of molecular sciences 20230110 2

The PRDM family of methyltransferases has been implicated in cellular proliferation and differentiation and is deregulated in human diseases, most notably in cancer. PRDMs are related to the SET domain family of methyltransferases; however, from the 19 PRDMs only a few PRDMs with defined enzymatic activities are known. PRDM15 is an uncharacterized transcriptional regulator, with significant structural disorder and lack of defined small-molecule binding pockets. Many aspects of PRDM15 are yet unk ...[more]

PMID: 36674842

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Project description:ImportanceCurrently, clinical assessment of olfaction is largely reliant on subjective methods that require patient participation. The objective method for measuring olfaction, using electroencephalogram (EEG) readings, can be supplemented with the improved temporal resolution of magnetoencephalography (MEG) for olfactory measurement that can delineate cortical and peripheral olfactory loss. MEG provides high temporal and spatial resolution which can enhance our understanding of central olfactory processing compared to using EEG alone.ObjectiveTo determine the feasibility of building an in-house portable olfactory stimulator paired with electrophysiological neuroimaging technique with MEG to assess olfaction in the clinical setting.Design setting and participantsThis proof-of-concept study utilized a paired MEG-olfactometer paradigm to assess olfaction in three normosmic participants. We used a two-channel olfactory stimulator to deliver odorants according to a programmed stimulus-rest paradigm. Two synthetic odorants: 2% phenethyl alcohol (rose) and 0.5% amyl acetate (banana) were delivered in increasing increments of time followed by periods of rest. Cortical activity was measured via a 306-channel MEG system.Main outcomes and measuresPrimary outcome measure was the relative spectral power for each frequency band, which was contrasted between rest and olfactory stimulation.ResultsCompared to rest, olfactory stimulation produced a 40% increase in relative alpha power within the olfactory cortex bilaterally with both odorants. A 25%-30% increase in relative alpha power occurred in the left orbitofrontal cortex and precentral gyrus with phenethyl alcohol stimulation but not amyl acetate.Conclusion and relevanceIn this proof-of-concept study, we demonstrate the feasibility of olfactory measurement via an olfactometer-MEG paradigm. We found that odorant-specific cortical signatures can be identified using this paradigm, setting the basis for further investigation of this system as a prognostic tool for olfactory loss.

Dataset Information

Proof-of-Concept Method to Study Uncharacterized Methyltransferases Using PRDM15.

Publications

Proof-of-Concept Method to Study Uncharacterized Methyltransferases Using PRDM15.

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