A tissue-specific promoter derived from a SINE retrotransposon drives biallelic expression of PLAGL1 in human lymphocytes

• Published in: PloS one Vol. 12; no. 9; p. e0185678
• Main Authors: Smith, Claire E. L., Alexandraki, Alexia, Cordery, Sarah F., Parmar, Rekha, Bonthron, David T., Valleley, Elizabeth M. A.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.09.2017; Public Library of Science (PLoS)
• Subjects: Alleles; Apoptosis; B-Lymphocytes - metabolism; Biology and life sciences; Cell cycle; Cell Cycle Proteins - genetics; Chromosome 6; CpG Islands; Diabetes; Diabetes mellitus; Epigenetics; Fetuses; Gene expression; Genetic aspects; Genomes; Human tissues; Humans; Leukocytes; Lymphocytes; Lymphocytes T; Medicine; Medicine and Health Sciences; Neonates; Peripheral blood; Physiological aspects; Promoter Regions, Genetic; Real-Time Polymerase Chain Reaction; Research and Analysis Methods; Retroelements; Retrotransposons; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Short Interspersed Nucleotide Elements - genetics; T-Lymphocytes - metabolism; Tissues; Transcription; Transcription Factors - genetics; Transcription, Genetic; Tumor Suppressor Proteins - genetics; Tumorigenesis; United Kingdom
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0185678

The imprinted gene PLAGL1 is an important regulator of apoptosis and cell cycle arrest. Loss of its expression has been implicated in tumorigenesis in a range of different cancers, and overexpression during fetal development causes transient neonatal diabetes mellitus (TNDM). PLAGL1 lies within an imprinted region of chromosome 6q24, and monoallelic expression from the major, differentially methylated promoter (P1) occurs in most human tissues. However, in peripheral blood leukocytes, the active promoter (P2) is non-imprinted and drives biallelic transcription. We report here a novel PLAGL1 promoter (P5) derived from the insertion of a primate-specific, MIR3 SINE retrotransposon. P5 is highly utilized in lymphocytes, particularly in T cells, and like P2, directs biallelic transcription. Our results show that it is important to consider P5 in relation to PLAGL1 function in T cells when investigating the dysregulation of this gene.