Transkript signature

In a biological context, a transcript signature refers to a characteristic pattern of specific gene expression. As a genetic signature, the transcript signature indicates which genes are upregulated or downregulated in a certain situation, e.g. in an inflammatory skin disease, i.e. their activity level.

Transcription itself is a molecular biological process in which the genetic information of a gene is transferred from the DNA to an mRNA copy. The term "signature" in this context refers to the specific process of initiation in which the RNA polymerase binds to the promoter of the gene to start the process of transcription. For example, in bacteria, the so-called sigma factor is the main factor that enables binding to the promoter and thus positions the RNA polymerase, whereas in eukaryotes complex sets of general transcription factors are required.

The transcriptional output of a cell is largely determined by the active enhancer elements contained in its genome. Enhancers were first described as DNA sequences in the 1980s. They increase the expression of a linked gene regardless of its distance and orientation (Moreau P et al. 1981).

For example, systemic lupus erythematosus (SLE) has a characteristic interferon (IFN) signature. IFN types, both individually and in combination, define different clinical and molecular subtypes in SLE. Thus, high IFN-II/-III levels without IFN-I had little effect on disease activity, IFN-II was associated with IFN-I-independent transcriptional profiles (e.g. OXPHOS and CD8 ⁺ GZMH ⁺ cells), and IFN-III enhanced IFN-induced gene expression when concomitantly increased with IFN-I (Gómez-Bañuelos E et al. 2024).

In a non-medical context, a transcript signature is also referred to as the insertion of a digital signature into a document.

1. Lewis MW et Al: (2019) Transcriptional control by enhancers and enhancer RNAs. Transcription 10(4-5):171-186.
2. Liu F (2017) Enhancer-derived RNA: A Primer. Genomics Proteomics Bioinformatics 15:196-200.
3. Moreau P et al. (1981) The SV40 72 base repair repeat has a striking effect on gene expression both in SV40 and other chimeric recombinants. Nucleic Acids Res 9:6047-6068.
4. Ryan RJ et al. (2015) Detection of Enhancer-Associated Rearrangements Reveals Mechanisms of Oncogene Dysregulation in B-cell Lymphoma. Cancer Discov 5:1058-1071.
5. Sur I et al. (2016) The role of enhancers in cancer. Nat Rev Cancer 16:483-93
6. Gómez-Bañuelos E et al. (2024) Uncoupling interferons and the interferon signature explains clinical and transcriptional subsets in SLE. Cell Rep Med 5:101569.