title: An intragenic long noncoding RNA interacts epigenetically with the RUNX1 promoter and enhancer chromatin DNA in hematopoietic malignancies.
abstract: 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.
authors.affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, People's Republic of China; VA Palo Alto Health Care System and Stanford University Medical School, Palo Alto, CA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Jingnan
authors.initials: J
authors.lastname: Sun
authors.forename: Jiuwei
authors.initials: J
authors.lastname: Cui
authors.forename: Guanjun
authors.initials: G
authors.lastname: Wang
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hoffman
authors.forename: Ji-Fan
authors.initials: JF
authors.lastname: Hu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry*; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000648:ultrastructure; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D003561:Cytarabine / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D004742:Enhancer Elements, Genetic; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D059472:Exome; D015973:Gene Expression Regulation, Leukemic; D006367:HeLa Cells; D019337:Hematologic Neoplasms / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D009154:Mutation; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D000970:Antineoplastic Agents; D002843:Chromatin; D050676:Core Binding Factor Alpha 2 Subunit; D062085:RNA, Long Noncoding; C493728:RUNX1 protein, human; D003561:Cytarabine; D004247:DNA; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
keywords: RUNX1; RUNXOR; chromosomal translocation; epigenetics; intrachromosomal interaction; leukemia; long noncoding RNA