Analytical epigenetics: single-molecule optical detection of DNA and histone modifications

Abstract

The field of epigenetics describes the relationship between genotype and phenotype, by regulating gene expression without changing the canonical base sequence of DNA. It deals with molecular genomic information that is encoded by a rich repertoire of chemical modifications and molecular interactions. This regulation involves DNA, RNA and proteins that are enzymatically tagged with small molecular groups that alter their physical and chemical properties. It is now clear that epigenetic alterations are involved in development and disease, and thus, are the focus of intensive research. The ability to record epigenetic changes and quantify them in rare medical samples is critical for next generation diagnostics. Optical detection offers the ultimate single-molecule sensitivity and the potential for spectral multiplexing. Here we review recent progress in ultrasensitive optical detection of DNA and histone modifications.

Single-molecule optical genome mapping in nanochannels: multidisciplinarity at the nanoscale

“…The epigenetic information is crucial for regulating specific cell functions [ 89 ]. Major epigenetic mechanisms include covalent modifications of DNA bases [ 90–92 ] and histones [ 92 , 93 ], chromatin structure [ 89 , 93 , 94 ] and noncoding RNAs that can control gene expression [ 95 ]. Unlike the genetic code, which is essentially stable throughout life, the epigenetic content is dynamically changing in response to environmental cues and has great impact on cell activity and diseases [ 96 ].…”

Electrochemical DNA Biosensors Based on the Intrinsic Topological Insulator BiSbTeSe2 for Potential Application in HIV Determination

“…Therefore, it is necessary to develop a sensitive, selective, and accurately quantitative method to determine the DNA series for infection diagnosis. Various DNA diagnosis methods have been developed, including polymerase chain reaction (PCR), − optics, − electrochemistry, − electrogenerated chemiluminescence (ECL), − and electrochemical biosensors. − Among various methods for biomolecule detection, electrochemical biosensors have many advantages, such as easy and fast operation, high sensitivity, and simple data analysis. − To develop high-performance electrochemical biosensors, it is essential to use electrodes with high electron conductivity to promote interfacial charge transfer and strong stability to provide reliable results. Recently, topological insulators (TIs) have been used as electrochemical electrode materials to make a sensitive DNA detector .…”

Label as you fold: methyltransferase-assisted functionalization of DNA nanostructures

“…When chemically modified cofactors are supplied, methyltransferases can also transfer other chemical moieties, which was termed "methyltransferase-directed transfer of activated groups" (mTAG). [14][15][16][17] An azide-carrying cofactor, for example, enables the sequence-specific, covalent introduction of azide groups into DNA. 18,19 More or less arbitrary functional groups can be attached to these universal linkage points via click chemistry.…”