Biology subjects

Yutaka Suzuki

Publications and source records attributed to Yutaka Suzuki.

3 recordsLinked to original sources

bioRxiv2016

Waves of chromatin modifications in mouse dendritic cells in response to LPS stimulation

BackgroundThe importance of transcription factors (TFs) and epigenetic modifications in the control of gene expression is widely accepted. However, causal relationships between changes in TF binding, histone modifications, and gene expression during the response to extracellular stimuli are not well understood. Here, we analyzed the ordering of these events on a genome-wide scale in dendritic cells (DCs) in response to lipopolysaccharide (LPS) stimulation.\n\nResultsUsing a ChIP-seq time series dataset, we found that the LPS-induced accumulation of different histone modifications follow clearly distinct patterns. Increases in H3K4me3 appear to coincide with transcriptional activation. In contrast, H3K9K14ac accumulates early after stimulation, and H3K36me3 at later time points. Integrative analysis with TF binding data revealed potential links between TF activation and dynamics in histone modifications. Especially, LPS-induced increases in H3K9K14ac and H3K4me3 were associated with binding by STAT1/2, and were severely impaired in Stat1-/- cells.\n\nConclusionsWhile the timing of short-term changes of some histone modifications coincides with changes in transcriptional activity, this is not the case for others. In the latter case, dynamics in modifications more likely reflect strict regulation by stimulus-induced TFs, and their interactions with chromatin modifiers.

Genomics↗

bioRxiv2016

Enhanced functional divergence of duplicate genes several million years after gene duplication in the Arabidopsis lineage

Lineage-specifically duplicated genes likely contribute to the phenotypic divergence in closely related species. However, neither the frequency of duplication events nor the degree of selective pressures immediately after gene duplication is clear in the speciation process. Plants have substantially higher gene duplication rates than most other eukaryotes. Here, using Illumina short reads from Arabidopsis halleri, which has highly qualified plant genomes in close species (Brassica rapa, A. thaliana and A. lyrata), we succeeded in generating orthologous gene groups among B. rapa, A. thaliana, A. lyrata and A. halleri. The frequency of duplication events in the Arabidopsis lineage was approximately 10 times higher than the frequency inferred by comparative genomics of Arabidopsis, poplar, rice and moss. Of the currently retained genes in A. halleri, 11-24% had undergone gene duplication in the Arabidopsis lineage. To examine the degree of selective pressure for duplicated genes, we calculated the ratios of nonsynonymous to synonymous substitution rates (KA/KS) in the A. halleri-lyrata and A. halleri lineages. Using a maximum-likelihood framework, we examined positive (KA/KS > 1) and purifying selection (KA/KS < 1) at a significant level (P < 0.01). Duplicate genes tended to have a higher proportion of positive selection compared with non-duplicated genes. More interestingly, we found that functional divergence of duplicated genes was accelerated several million years after gene duplication at a higher proportion than immediately after gene duplication.

Genomics↗

bioRxiv2016

Identification of physical interactions between genomic regions by enChIP-Seq

Physical interactions between genomic regions play critical roles in the regulation of genome functions, including gene expression. However, the methods for confidently detecting physical interactions between genomic regions remain limited. Here, we demonstrate the feasibility of using engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) in combination with next-generation sequencing (NGS) (enChIP-Seq) to detect such interactions. In enChIP-Seq, the target genomic region is captured by an engineered DNA-binding complex, such as a CRISPR system consisting of a catalytically inactive form of Cas9 (dCas9) and a single guide RNA (sgRNA). Subsequently, the genomic regions that physically interact with the target genomic region in the captured complex are sequenced by NGS. Using enChIP-Seq, we found that the 5HS5 locus, which regulates expression of the {beta}-globin genes, interacts with multiple genomic regions upon erythroid differentiation in the human erythroleukemia cell line K562. Genes near the genomic regions inducibly associated with the 5HS5 locus were transcriptionally up-regulated in the differentiated state, suggesting the existence of a coordinated transcription mechanism directly or indirectly mediated by physical interactions between these loci. Our data suggest that enChIP-Seq is a potentially useful tool for detecting physical interactions between genomic regions in a non-biased manner, which would facilitate elucidation of the molecular mechanisms underlying regulation of genome functions.

Molecular Biology↗