Transcriptional Regulation of lncRNA Genes by Histone Modification in Alzheimer’s Disease

Abstract

Increasing studies have revealed that long noncoding RNAs (lncRNAs) are not transcriptional noise but play important roles in the regulation of a wide range of biological processes, and the dysregulation of lncRNA genes is associated with disease development. Alzheimer's disease (AD) is a chronic neurodegenerative disease that usually starts slowly and gets worse over time. However, little is known about the roles of lncRNA genes in AD and how the lncRNA genes are transcriptionally regulated. Herein, we analyzed RNA-seq data and ChIP-seq histone modification data from CK-p25 AD model and control mice and identified 72 differentially expressed lncRNA genes, 4,917 differential peaks of H3K4me3, and 1,624 differential peaks of H3K27me3 between AD and control samples, respectively. Furthermore, we found 92 differential peaks of histone modification H3K4me3 are located in the promoter of 39 differentially expressed lncRNA genes and 8 differential peaks of histone modification H3K27me3 are located upstream of 7 differentially expressed lncRNA genes, which suggest that the majority of lncRNA genes may be transcriptionally regulated by histone modification in AD.

Upregulation of the lncRNA MEG3 improves cognitive impairment, alleviates neuronal damage, and inhibits activation of astrocytes in hippocampus tissues in Alzheimer's disease through inactivating the PI3K/Akt signaling pathway

“…lncRNAs impact the pathogenesis of AD mainly due to their diverse biochemical and functional effects, including posttranscriptional and posttranslational regulation, chromatin modulation as well as protein complex organization . However, how lncRNA genes are transcriptionally modulated in diseases such as AD remains to be known . On the basis of this, we launched this study to seek for the inner mechanisms of MEG3 in AD through the PI3/Akt signaling pathway.…”

“…Aβ [25][26][27][28][29][30][31][32][33][34][35] powder (1 mg; Lot: 111M4775V; 98% purity; Sigma Inc) dissolved by 0.5 mL sterile normal saline was prepared into a 2 μg/μL working fluid (3 nmol/uL), and then sealed and decomposed in a sterile incubator at 3°C for 1 week to produce Aβ [25][26][27][28][29][30][31][32][33][34][35] in an aggregate state. The rats were intraperitoneally injected with 1% pentobarbital sodium for anesthesia.…”

Long Non-Coding RNA ZEB1-Antisense 1 Affects Cell Migration and Invasion of Cervical Cancer by Regulating Epithelial-Mesenchymal Transition via the p38MAPK Signaling Pathway

“…With the widespread application of deep sequencing technology, lncRNA that was previously regarded as the "noise" in the transcription of genes, has been well recognized as an essential regulator involved in many biological processes of tumor cells, such as cell proliferation, cell cycle, apoptosis, metastasis and so on [22,23]. To date, approximately 7,000-23,000 lncRNAs were estimated to be existing in the human genome [24].…”

TGF‐β‐mediated exosomal lnc‐MMP2‐2 regulates migration and invasion of lung cancer cells to the vasculature by promoting MMP2 expression

“…Noncoding RNAs encoded by the eukaryotic genome comprise a large number of RNAs that are not translated into proteins. Accumulating evidence revealed major transcriptional and posttranscriptional regulatory roles of long noncoding (lnc)RNAs and include transcription‐factor recruitment, chromatin remodeling, histone modification, pre‐mRNA splicing, and as molecular sponges and scaffolds involved in the development of normal tissues or organs, as well as in carcinogenesis and the aggression of diverse malignancies …”

“…Accumulating evidence revealed major transcriptional and posttranscriptional regulatory roles of long noncoding (lnc)RNAs 16 and include transcription-factor recruitment, chromatin remodeling, histone modification, pre-mRNA splicing, and as molecular sponges and scaffolds involved in the development of normal tissues or organs, as well as in carcinogenesis and the aggression of diverse malignancies. 17,18 A previous study reported that TGF-β influences microRNA (miRNA) expression in exosomes 19 ; however, the role of TGF-β in promoting exosomal lncRNA expression has not been reported. Here, we performed coculture of TGF-β-treated A549 cells with lung cancer cells or lung microvascular endothelial cells to evaluate the TGF-β-mediated invasion ability of the lung cancer cells and changes in permeability of the vascular endothelial cell layer.…”