Noncoding RNA transcription at enhancers and genome folding in cancer

• Published in: Cancer science Vol. 110; no. 8; pp. 2328 - 2336
• Main Authors: Isoda, Takeshi, Morio, Tomohiro, Takagi, Masatoshi
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.08.2019; John Wiley and Sons Inc
• Subjects: Animals; cancer; Cell differentiation; Cell lineage; Cohesin; Demethylation; Deoxyribonucleic acid; DNA; DNA methylation; DNA-directed RNA polymerase; Enhancer Elements, Genetic - genetics; Enhancers; Gene expression; Gene loci; Genome - genetics; genome folding; Genomes; Humans; Immunoglobulins; Kinases; Leukemia; Localization; Lymphocytes; Lymphoma; Neoplasms - genetics; noncoding RNA; Phenotypes; Phosphorylation; Promoter Regions, Genetic - genetics; Proteins; Review; RNA polymerase; RNA, Untranslated - genetics; Severe combined immunodeficiency; ThymoD; transcription; Transcription factors; Transcription, Genetic - genetics; cancer; noncoding RNA; ThymoD; transcription; genome folding
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/cas.14107

Changes of nuclear localization of lineage‐specific genes from a transcriptionally inert to permissive environment are a crucial step in establishing the identity of a cell. Noncoding RNA transcription‐mediated genome folding and activation of target gene expression have been found in a variety of cell types. Noncoding RNA ThymoD (thymocyte differentiation factor) transcription at superenhancers is essential for mouse T‐cell lineage commitment. The cessation of ThymoD transcription abolishes transcription‐mediated demethylation, recruiting looping factors such as the cohesin complex, CCCTC‐binding factor (CTCF), ultimately leading to the phenotype of severe combined immunodeficiency and T‐cell leukemia/lymphoma. In this review, we describe the functional role of RNA polymerase II‐mediated transcription at enhancers and in genome folding. We also highlight the involvement of faulty activation or suppression of enhancer transcription and enhancer‐promoter interaction in cancer development. Noncoding RNA ThymoD (thymocyte differentiation factor) transcription at superenhancers is essential for mouse T‐cell lineage commitment. The cessation of ThymoD transcription abolishes transcription‐mediated demethylation, recruiting looping factors such as the cohesin complex, CTCF, ultimately leading to the phenotype of severe combined immunodeficiency and T‐cell leukemia/lymphoma.