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Differences in genomic epigenetic signatures of coding and long non-coding RNA genes in mouse erythroblasts and megakaryocytes

Monday, September 22, 2014 — Poster Session I

12:00 p.m. – 2:00 p.m.

FAES Academic Center




  • E.F. Heuston
  • J. Lichtenberg
  • S.M. Anderson
  • M. Kirby
  • C.K. Capone
  • V. Paralkar
  • R.C. Hardison
  • M. Weiss
  • D.M. Bodine


The ENCODE project provided an epigenetic roadmap of DNA methylation (CH3) and transcription factor (TF) occupancy in non-differentiating cell lines, but not in primary cells. We hypothesize that the closely related erythroblast (EB) and megakaryocyte (MK) lineages develop differentiation-specific epigenetic profiles. To test this hypothesis we isolated EBs and MKs from mouse bone marrow and performed MethylSeq, ChIPSeq, and RNASeq to map and correlate genome-wide CH3, TF occupancy, and novel coding (mRNA) and long non-coding (lncRNA) transcript expression. Our data demonstrate that CH3 localization distinguishes between mRNAs and lncRNAs: >41% of mRNAs have gene body CH3, whereas >30% of lncRNAs have upstream/downstream CH3 (p <0.0001). TFs, however, distinguish between EBs and MKs: 79% of GATA1 sites are EB-specific, and 72% of NFE2 sites are MK-specific. In correlating these profiles we found that 38% of EB mRNA gene bodies have GATA1 occupancy and CH3, 81% of which are transcriptionally silent. In contrast, 42% of MK mRNA gene bodies have NFE2 occupancy and CH3; 80% of these genes are expressed. These repressed EB and active MK genes influence similar cell functions including nucleic acid metabolism and organismal survival (p <0.008), reflecting the contrasting EB (post-mitotic) and MK (pre-endomitotic) cellular fates.

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