Integrated analysis of DNA methylation and RNA‑sequencing data in Down syndrome.
Down syndrome (DS) is the most common birth defect in children. To investigate the mechanisms of DS, the present study analyzed the bisulfite‑sequencing (seq) data GSE42144, which was downloaded from the Gene Expression Omnibus. GSE42144 included DNA methylation data of three DS samples and three control samples, and RNA‑seq data of two DS samples and five control samples. The methylated sites in the bisulfite‑seq data were detected using Bismark and Bowtie2. The BiSeq tool was applied to determine differentially methylated regions and to identify adjacent genes. Using the Database for Annotation, Visualization and Integrated Discovery, the functions of the abnormal demethylated genes were predicted by functional enrichment analyses. Differentially expressed genes (DEGs) were then screened using a paired t‑test. Furthermore, the interactions of the proteins encoded by selected genes were determined using the Search Tool for the Retrieval of Interacting Genes, and a protein‑protein interaction (PPI) network was constructed using Cytoscape. A total of 74 CpG regions showed significant differential DNA methylation between the DS and normal samples. There were five abnormal demethylated DNA regions in chromosome 21. In the DS samples, a total of 43 adjacent genes were identified with demethylation in their promoter regions and one adjacent gene was identified with upregulated methylation in its promoter regions. In addition, 584 upregulated genes were identified, including 24 genes with transcriptional regulatory function. In particular, upregulated Runt‑related transcription factor 1 (RUNX1) was located on chromosome 21. Functional enrichment analysis indicated that inhibitor of DNA binding 4 (ID4) was involved in neuronal differentiation and transcriptional suppression. In the PPI network, genes may be involved in DS by interacting with others, including nuclear receptor subfamily 4 group A member 2 (NR4A2)‑early growth response (EGR)2 and NR4A2‑EGR3. Therefore, RUNX1, NR4A2, EGR2, EGR3 and ID4 may be key genes associated with the pathogenesis of DS.
Department of Colorectal Anal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Jiantao
J
Zhang
Department of Neonatology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Wenli
W
Zhou
Department of Neonatology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Ying
Y
Liu
Department of Neonatology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Nan
N
Li
D019295:Computational Biology; D050676:Core Binding Factor Alpha 2 Subunit / Q000096:biosynthesis / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D030541:Databases, Genetic; D004314:Down Syndrome / Q000235:genetics* / Q000473:pathology; D051767:Early Growth Response Protein 2 / Q000096:biosynthesis / Q000235:genetics*; D051776:Early Growth Response Protein 3 / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000096:biosynthesis / Q000235:genetics*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000096:biosynthesis / Q000235:genetics*; D060066:Protein Interaction Maps / Q000235:genetics; D017423:Sequence Analysis, RNA; D015398:Signal Transduction
D050676:Core Binding Factor Alpha 2 Subunit; C497326:EGR2 protein, human; C079945:EGR3 protein, human; D051767:Early Growth Response Protein 2; C490128:ID4 protein, human; D051796:Inhibitor of Differentiation Proteins; C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; C493728:RUNX1 protein, human; D051776:Early Growth Response Protein 3