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	NHGRI	DEVBIO-4

Authors

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

Abstract

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.

back to top