Abstract
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.
Highlights
Genomic imprinting is an epigenetic process by which specific genes are expressed preferentially according to their parent of origin
The present work was prompted by the existence of three novel spliced Pleomorphic adenoma gene-like 1 (PLAGL1) expressed sequence tag (EST) that appear to initiate at a novel genomic location lying between the differentially methylated (P1) promoter and the upstream, unmethylated promoter (P2)
These ESTs range in length from 519-560-bp and were derived from peripheral blood mononuclear cells, thymus (DB104173) and kidney tumour tissue (DB177852) [10]
Summary
Genomic imprinting is an epigenetic process by which specific genes are expressed preferentially according to their parent of origin. At a biochemical and cellular level, PLAGL1 protein both acts as a transcriptional co-activator for p53 and regulates cell cycle and apoptosis concomitantly [2,3]. Dysregulation of this gene plays a pathogenic role in the tumorigenesis of several types of cancer and in a rare form of childhood diabetes, transient neonatal diabetes mellitus (TNDM1; OMIM #601410) [4]. To be a “micro-imprinted” domain [6] It contains a differentially methylated region (DMR) that acts as a promoter (P1) directing transcription from the unmethylated, paternal allele in most human and mouse tissues [2]. We have identified a fifth promoter region (P5), from which transcripts are highly expressed in lymphocytes, T cells
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