An intragenic long noncoding RNA interacts epigenetically with the RUNX1 promoter and enhancer chromatin DNA in hematopoietic malignancies

Int J Cancer. 2014 Dec 15;135(12):2783-94. doi: 10.1002/ijc.28922. Epub 2014 May 2.


RUNX1, a master regulator of hematopoiesis, is the most commonly perturbed target of chromosomal abnormalities in hematopoietic malignancies. The t(8;21) translocation is found in 30-40% of cases of acute myeloid leukemia (AML). Recent whole-exome sequencing also reveals mutations and deletions of RUNX1 in some solid tumors. We describe a RUNX1-intragenic long noncoding RNA RUNXOR that is transcribed as unspliced transcript from an upstream overlapping promoter. RUNXOR was upregulated in AML samples and in response to Ara-C treatment in vitro. RUNXOR utilizes its 3'-terminal fragment to directly interact with the RUNX1 promoter and enhancers and participates in the orchestration of an intrachromosomal loop. The 3' region of RUNXOR also participates in long-range interchromosomal interactions with chromatin regions that are involved in multiple RUNX1 translocations. These data suggest that RUNXOR noncoding RNA may function as a previously unidentified candidate component that is involved in chromosomal translocation in hematopoietic malignancies.

Keywords: RUNX1; RUNXOR; chromosomal translocation; epigenetics; intrachromosomal interaction; leukemia; long noncoding RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Chromatin / chemistry*
  • Chromosome Aberrations
  • Chromosomes / ultrastructure
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Cytarabine / chemistry
  • DNA / chemistry
  • Enhancer Elements, Genetic*
  • Enhancer of Zeste Homolog 2 Protein
  • Epigenesis, Genetic*
  • Exome
  • Gene Expression Regulation, Leukemic
  • HeLa Cells
  • Hematologic Neoplasms / metabolism*
  • Humans
  • K562 Cells
  • Leukemia, Myeloid, Acute / genetics
  • Mutation
  • Polycomb Repressive Complex 2 / metabolism
  • Promoter Regions, Genetic*
  • RNA, Long Noncoding / genetics*
  • Translocation, Genetic


  • Antineoplastic Agents
  • Chromatin
  • Core Binding Factor Alpha 2 Subunit
  • RNA, Long Noncoding
  • RUNX1 protein, human
  • Cytarabine
  • DNA
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2