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Reduced methyl-CpG protein binding contributing to miR-184 expression in umbilical cord blood CD4+ T-cells

Leukemia volume 25, pages 169–172 (2011)Cite this article

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Numerous studies by our group and others confirm blunted allogeneic responses by umbilical cord blood (UCB) graft CD4+ T-cells.1 This may be attributable in part to dramatically reduced NFAT1 protein without corresponding mRNA discrepancies.2 We have previously shown that microRNA-184 (miR-184) mediates NFAT1 translational regulation in UCB CD4+ T-cells.3 In humans, miR-184 resides within region 25.1 on the q-arm of chromosome 15 and exhibits characteristics that are uncommon to many other intergenic miRNA species. Specifically, its transcript is comparatively small (84 bp) and is not encoded near other clustered miRNAs.

A recent report has identified DNA methylation patterns and the methyl-CpG binding protein MeCP2 during polarization and imprinting as relevant to miR-184 expression in murine brain.4 MeCP2 is hypothesized to bind differentially to hemi-methylated regions or specific CpG sites, resulting in transcriptional repression via recruitment of histone-modifying enzymes or other mechanisms.5 Although the region containing miR-184 on murine chromosome 9E3.1 exhibits a very high degree of sequence homology to the miR-184 region on human 15q25.1, little is known about regulation of miR-184 expression in human T-lymphocytes. Here we identify the epigenetic mechanisms underlying miR-184 regulation in human CD4+ T-cells.

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Acknowledgements

This work was supported by the Abraham J and Phyllis Katz Foundation, and the Dr Donald and Ruth Weber Goodman Philanthropic Fund through the Cleveland Cord Blood Center (MJL). We thank Y-C Yang, Q Li and the CWRU Department of Genetics Sequencing Core for technical assistance. We are grateful for the review and advice of Drs Yang, H Meyerson and A Levine.

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Authors and Affiliations

  1. Department of Pathology, Case Western Reserve University, Cleveland, OH, USA

    R P Weitzel & M J Laughlin

  2. Department of Medicine, Case Western Reserve University, Cleveland, OH, USA

    R P Weitzel, M L Lesniewski, N J Greco & M J Laughlin

  3. Cleveland Cord Blood Center, Cleveland, OH, USA

    N J Greco & M J Laughlin

  4. Department of Medicine, University of Virginia, Charlottesville, VA, USA

    M J Laughlin

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  1. R P Weitzel
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  2. M L Lesniewski
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  3. N J Greco
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  4. M J Laughlin
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Correspondence to M J Laughlin.

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Weitzel, R., Lesniewski, M., Greco, N. et al. Reduced methyl-CpG protein binding contributing to miR-184 expression in umbilical cord blood CD4+ T-cells. Leukemia 25, 169–172 (2011). https://doi.org/10.1038/leu.2010.227

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