Epigenetic regulation of human-specific gene expression in the prefrontal cortex.

BACKGROUND: Changes in gene expression levels during brain development are thought to have played an important role in the evolution of human cognition. With the advent of high-throughput sequencing technologies, changes in brain developmental expression patterns, as well as human-specific brain gene expression, have been characterized. However, interpreting the origin of evolutionarily advanced cognition in human brains requires a deeper understanding of the regulation of gene expression, including the epigenomic context, along the primate genome. Here, we used chromatin immunoprecipitation sequencing (ChIP-seq) to measure the genome-wide profiles of histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 acetylation (H3K27ac), both of which are associated with transcriptional activation in the prefrontal cortex of humans, chimpanzees, and rhesus macaques. RESULTS: We found a discrete functional association, in which H3K4me3HP gain was significantly associated with myelination assembly and signaling transmission, while H3K4me3HP loss played a vital role in synaptic activity. Moreover, H3K27acHP gain was enriched in interneuron and oligodendrocyte markers, and H3K27acHP loss was enriched in CA1 pyramidal neuron markers. Using strand-specific RNA sequencing (ssRNA-seq), we first demonstrated that approximately 7 and 2% of human-specific expressed genes were epigenetically marked by H3K4me3HP and H3K27acHP, respectively, providing robust support for causal involvement of histones in gene expression. We also revealed the co-activation role of epigenetic modification and transcription factors in human-specific transcriptome evolution. Mechanistically, histone-modifying enzymes at least partially contribute to an epigenetic disturbance among primates, especially for the H3K27ac epigenomic marker. In line with this, peaks enriched in the macaque lineage were found to be driven by upregulated acetyl enzymes. CONCLUSIONS: Our results comprehensively elucidated a causal species-specific gene-histone-enzyme landscape in the prefrontal cortex and highlighted the regulatory interaction that drove transcriptional activation.

Analysis of long noncoding RNAs expression profiles in the human cardiac fibroblasts with cardiac fibrosis.

Cardiac fibrosis is a common pathological feature of cardiac remodelling process with disordered expression of multiple genes and eventually lead to heart failure. Emerging evidence suggests that long noncoding RNAs (lncRNAs) have emerged as critical regulators of various biological processes. However, the exact mechanisms of lncRNAs as mediators in cardiac fibrosis have not been fully elucidated. This study aimed to profile the lncRNA expression pattern in human cardiac fibroblasts (HCFs) with cardiac fibrosis. We treated HCFs with transforming growth factor-ß (TGF-ß) to induce their activation. Then, strand-specific RNA-seq was performed to profile and classify lncRNAs; and perform functional analysis in HCFs. We study the transformation of HCFs with molecular and cell biology methods. Among all identified lncRNA candidates, 176 and 526 lncRNAs were upregulated and downregulated respectively in TGF-ß-stimulated HCFs compared with controls. Functional analyses revealed that the target genes of differentially expressed lncRNAs were mainly related to focal adhesion, metabolic pathways, Hippo signaling pathway, PI3K-Akt signaling pathway, regulation of actin cytoskeleton, and hypertrophic cardiomyopathy. As a representative, novel lncRNAs NONHSAG005537 and NONHSAG017620 inhibited the proliferation, migration, invasion, and transformation of HCFs induced by TGF-ß. Collectively, our study established the expression signature of lncRNAs in cardiac fibrosis and demonstrated the cardioprotective role of NONHSAG005537 and NONHSAG017620 in cardiac fibrosis, providing a promising target for anti-fibrotic therapy.

Genome-wide analysis of rice cis-natural antisense transcription under cadmium exposure using strand-specific RNA-Seq.

BACKGROUND: The elucidation of novel transcripts and their expression in response to various stress conditions is necessary to understand the transcriptional network of plants as an adaptation to biotic and abiotic stresses. We performed strand-specific RNA-Seq (ssRNA-Seq) on rice exposed to cadmium (Cd) for 24 h and investigated the expression of cis-natural antisense transcripts (cis-NATs), a class of endogenous coding or non-protein-coding RNAs with sequence complementarity to the opposite strands of RAP transcripts. RESULTS: Many RAP transcripts possessed cis-NATs and these cis-NATs were responsive to some extent. Cis-NATs were upregulated from 26, 266 and 409 RAP gene loci, while 2054, 2501 and 2825 RAP transcripts were upregulated from 38,123 RAP loci under high Cd exposure in roots at 1, 12 and 24 h, respectively. In addition, most of the upregulated cis-NATs showed little upregulation under ABA or cold treatment. A number of cis-NATs were upregulated from less than 35 RAP gene loci in different tissue and time-point combinations under low Cd exposure, suggesting that cis-NATs respond to environmental stress. Furthermore, 409 RAP transcripts with upregulated cis-NATs were classified into three groups based on the expression of the RAP transcripts from the opposite DNA strand, including 138 upregulated, 128 invariable, and 143 downregulated transcripts, although the responses of cis-NATs and RAP transcripts were not always correlated. CONCLUSIONS: We have shown that the cis-NATs identified by ssRNA-Seq analysis are novel genes and that some of them are stress-specific and show different responses depending on the degree of stress and tissue. These results improve our understanding of the complete molecular mechanism of plant adaptation to Cd exposure.