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Publication : Tissue-restricted transcription from a conserved intragenic CpG island in the Klf1 gene in mice.

First Author  Southwood CM Year  2012
Journal  Biol Reprod Volume  87
Issue  5 Pages  108
PubMed ID  22933519 Mgi Jnum  J:192480
Mgi Id  MGI:5465236 Doi  10.1095/biolreprod.112.099879
Citation  Southwood CM, et al. (2012) Tissue-restricted transcription from a conserved intragenic CpG island in the Klf1 gene in mice. Biol Reprod 87(5):108
abstractText  Beyond Mendelian inheritance, an understanding of the complexities and consequences of the transfer of nonhereditary information to successive generations is at an early stage. Such epigenetic functionality is exemplified by DNA methylation and, as genome-wide high-throughput methodologies emerge, is increasingly being considered in the context of conserved intragenic and intergenic CpG islands that function as alternate sites of transcription initiation. Here we characterize an intragenic CpG island in exon 2 of the protein-coding mouse Klf1 gene, from which clustered transcription initiation sites yield positive-strand, severely truncated, capped and spliced RNAs. Expression from this CpG island in the testis begins between Postnatal Days 14-20, increases during development, and is temporally correlated with the maturation of secondary spermatocytes as they become the dominant cell population in the seminiferous epithelium. Only full-length KLF1-encoding mRNAs are detected in the hematopoietic tissue, spleen; thus, expression from the exon 2 CpG island is both developmentally regulated and tissue restricted. DNA methylation analysis indicates that spatiotemporal expression from the Klf1 CpG island is not associated with hypermethylation. Finally, our computational analysis from multiple species confirms intragenic transcription initiation and indicates that the KLF1 CpG island is evolutionarily conserved. Currently we have no evidence that these truncated RNAs can be translated via nonconventional mechanisms such as in-frame, conserved non-AUG-dependent Kozak consensus sequences; however, high-quality carboxyl-terminal antibodies will more effectively address this issue.
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