鉴定 RUNX1 内含子 5 内的一个新型长非编码 RNA。

Identification of a novel long non-coding RNA within RUNX1 intron 5.

机构信息

Laboratory of Epigenetics [EpiGene], Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario s/n, Concepción, Chile.

出版信息

Hum Genomics. 2019 Jul 31;13(1):33. doi: 10.1186/s40246-019-0219-1.

DOI:10.1186/s40246-019-0219-1

PMID:31366376

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6670153/

Abstract

BACKGROUND

RUNX1 gene, a master regulator of the hematopoietic process, participates in pathological conditions as a partner for several genes in chromosomal translocations. One of the most frequent chromosomal translocations found in acute myeloid leukemia patients is the t(8;21), in which RUNX1 and ETO genes recombine. In RUNX1 gene, the DNA double-strand breaks that originate the t(8;21) are generated in the intron 5, specifically within three regions designated as BCR1, BCR2, and BCR3. To date, what determines that these regions are more susceptible to DNA double-strand breaks is not completely clear. In this report, we characterized RUNX1 intron 5, by analyzing DNase-seq and ChIP-seq data, available in the ENCODE Project server, to evaluate DNaseI hypersensitivity and the presence of the epigenetic mark H3K4me3 in 124 and 51 cell types, respectively.

RESULTS

Our results show that intron 5 exhibits an epigenetic mark distribution similar to known promoter regions. Moreover, using the online tool YAPP and available CAGE data from the ENCODE Project server, we identified several putative transcription start sites within intron 5 in regions BCR2 and BCR3. Finally, available EST data was analyzed, identifying a novel uncharacterized long non-coding RNA, which is expressed in hematopoietic cell lines as shown by RT-PCR. Our data suggests that the core promoter of the novel long non-coding RNA locates within the region BCR3.

CONCLUSION

We identified a novel long non-coding RNA within RUNX1 intron 5, transcribed from a promoter located in the region BCR3, one of the chromosomal breakpoints of RUNX1 gene.

摘要

背景

RUNX1 基因是造血过程的主调控因子，作为染色体易位中几个基因的伙伴，参与病理状态。在急性髓系白血病患者中发现的最常见的染色体易位之一是 t(8;21)，其中 RUNX1 和 ETO 基因重组。在 RUNX1 基因中，导致 t(8;21)的 DNA 双链断裂是在内含子 5 中产生的，具体来说是在三个区域内产生的，称为 BCR1、BCR2 和 BCR3。迄今为止，是什么决定了这些区域更容易受到 DNA 双链断裂的影响还不完全清楚。在本报告中，我们通过分析 ENCODE 项目服务器中提供的 DNase-seq 和 ChIP-seq 数据来表征 RUNX1 内含子 5，以评估 DNaseI 超敏性和表观遗传标记 H3K4me3 在 124 和 51 种细胞类型中的存在情况。

结果

我们的结果表明，内含子 5 表现出与已知启动子区域相似的表观遗传标记分布。此外，使用在线工具 YAPP 和 ENCODE 项目服务器中提供的 CAGE 数据，我们在 BCR2 和 BCR3 区域的内含子 5 中鉴定出几个潜在的转录起始位点。最后，分析了可用的 EST 数据，鉴定出一种新型未表征的长非编码 RNA，如 RT-PCR 所示，在造血细胞系中表达。我们的数据表明，新型长非编码 RNA 的核心启动子位于 BCR3 区域内。