Come Visit Us at AACR! Booth #2141.

Overview of Transcriptional Misregulation in Cancer

Jump to Antibodies

 

Transcription factors are key regulators of gene transcription in eukaryotes. These proteins bind to specific DNA sequences in the 5’ region of a gene known as the promoter or enhancer region. The structure of a transcription factor consists of a DNA binding domain that interacts with the genome, and other domains that interact with other transcription factors, coactivators, RNA polymerases, silencers, and enhancers. Enhancers may initially bind to a region of the genome far from the gene they enhance, and bind to the transcription factor complex through chromatin looping1. Some components of a transcription factor complex are specific to the gene being primed for transcription and other components may be tissue-specific2. Or, transcription factors may be able to recognize several genes, but the target genes are expressed in a tissue-specific manner3.

 

Transcription factors can be grouped into families and there are four common DNA binding domain structures that exist in eukaryotes. These motifs are basic helix-loop-helix (consisting of a DNA-binding helix), helix-turn-helix (comprising a bundle of three helices), zinc finger (for which the DNA-binding helices require the presence of a zinc ion), and leucine zipper (in which a chain of leucine amino acids holds together two halves of a DNA-binding dimer)4,5. Basic helix-loop-helix transcription factors can be further subdivided into six subclasses based on the DNA and/or protein sequences they are able to bind. Common basic helix-loop-helix transcription factors include Myc, HIF, and MyoD6. The helix-turn-helix motif has evolved over time and is found in both prokaryotes and eukaryotes and in proteins besides transcription factors as well. Some common helix-turn-helix transcription factors include Cyclin, Myb, and BRCA25. Zinc finger domains are similarly present in transcription factors and other proteins that help to regulate cell cycle progression including apoptosis and protein folding7. Zinc finger transcription factors are also easily engineered to recognize any 18-base pair-long sequence of DNA to experimentally drive transcription of a specific gene8. Leucine zipper transcription factors are found exclusively in eukaryotes – both animals and plants9. A common class of leucine zipper transcription factors are the C/EBP proteins, which were the first to be identified with this motif10.

 

The requirement for transcription factor complexes, and not a single transcription factor binding to a gene, to initiate transcription is one way this process is regulated. Additionally, transcriptional repressors, or proteins that bind to transcription factor complexes and inhibit gene transcription, is another method of regulation. Transcriptional repressors may bind to a specific DNA sequence, or may bind as part of a complex11. Unlike activators of transcription that may bind at the gene site or elsewhere in the genome, repressors are most frequently observed to bind in the 5’ region of the gene being repressed4. Repressors also play other roles in the regulation of transcription. They have been implicated in priming genes for future transcription, retaining RNA polymerase at a gene site, and as co-regulators in association with transcriptional activators12.

 

Below is the entire list of targets involved in Cancer Transcriptional Misregulation research. Can’t find what you are looking for? Bethyl offers a custom antibody service.

 

References

1. Shlyueva D, Stampfel G, Stark A (2014) Transcriptional enhancers: from properties to genome-wide predictions. Nat Rev Genet 15:272–286 . doi: 10.1038/nrg3682

2. Levine M, Tjian R (2003) Transcription regulation and animal diversity. Nature 424:147–151 . doi: 10.1038/nature01763

3. Sonawane AR, Platig J, Fagny M, et al (2017) Understanding Tissue-Specific Gene Regulation. Cell Rep 21:1077–1088 . doi: 10.1016/j.celrep.2017.10.001

4. Phillips T, Hoopes L (2008) Transcription Factors and Transcriptional Control in Eukaryotic Cells. Nat Educ 1:119

5. ARAVIND L, ANANTHARAMAN V, BALAJI S, et al (2005) The many faces of the helix-turn-helix domain: Transcription regulation and beyond. FEMS Microbiol Rev 29:231–262 . doi: 10.1016/j.femsre.2004.12.008

6. Jones S (2004) An overview of the basic helix-loop-helix proteins. Genome Biol 5:226 . doi: 10.1186/gb-2004-5-6-226

7. Laity JH, Lee BM, Wright PE (2001) Zinc finger proteins: new insights into structural and functional diversity. Curr Opin Struct Biol 11:39–46 . doi: 10.1016/S0959-440X(00)00167-6

8. Beerli RR, Barbas CF (2002) Engineering polydactyl zinc-finger transcription factors. Nat Biotechnol 20:135–141 . doi: 10.1038/nbt0202-135

9. Nijhawan A, Jain M, Tyagi AK, Khurana JP (2008) Genomic survey and gene expression analysis of the basic leucine zipper transcription factor family in rice. Plant Physiol 146:333–50 . doi: 10.1104/pp.107.112821

10. Landschulz WH, Johnson PF, McKnight SL (1988) The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science 240:1759–64

11. Cooper GM (2000) Regulation of Transcription in Eukaryotes

12. Reynolds N, O’Shaughnessy A, Hendrich B (2013) Transcriptional repressors: multifaceted regulators of gene expression. Development 140:505–12 . doi: 10.1242/dev.083105