Genome-wide DNA methylation analysis reveals novel epigenetic changes in chronic lymphocytic leukemia

Lirong Pei, Jeong Hyeon Choi, Jimei Liu, Eun Joon Lee, Brian McCarthy, James M. Wilson, Ethan Speir, Farrukh Awan, Hongseok Tae, Gerald Arthur, Jennifer L. Schnabel, Kristen H. Taylor, Xinguo Wang, Dong Xu, Han Fei Ding, David H. Munn, Charles W. Caldwell, Huidong Shi

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

We conducted a genome-wide DNA methylation analysis in CD19+ B-cells from chronic lymphocytic leukemia (CLL) patients and normal control samples using reduced representation bisulfite sequencing (RRBS). The methylation status of 1.8-2.3 million CpGs in the CLL genome was determined; about 45% of these CpGs were located in more than 23,000 CpG islands (CGIs). While global CpG methylation was similar between CLL and normal B-cells, 1,764 gene promoters were identified as being differentially methylated in at least one CLL sample when compared with normal B-cell samples. Nineteen percent of the differentially methylated genes were involved in transcriptional regulation. Aberrant hypermethylation was found in all HOX gene clusters and a significant number of WNT signaling pathway genes. Hypomethylation occurred more frequently in the gene body including introns, exons and 3'-UTRs in CLL. The NFATc1 P2 promoter and first intron was found to be hypomethylated and correlated with upregulation of both NFATc1 RNA and protein expression levels in CLL suggesting that an epigenetic mechanism is involved in the constitutive activation of NFAT activity in CLL cells. This comprehensive DNA methylation analysis will further our understanding of the epigenetic contribution to cellular dysfunction in CLL.

Original languageEnglish (US)
Pages (from-to)567-578
Number of pages12
JournalEpigenetics
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 2012
Externally publishedYes

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Keywords

  • Chronic lymphocytic leukemia
  • DNA methylation
  • Next-generation sequencing
  • NFATc1
  • Reduced representation bisulfite sequencing

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Pei, L., Choi, J. H., Liu, J., Lee, E. J., McCarthy, B., Wilson, J. M., ... Shi, H. (2012). Genome-wide DNA methylation analysis reveals novel epigenetic changes in chronic lymphocytic leukemia. Epigenetics, 7(6), 567-578. https://doi.org/10.4161/epi.20237