Project description:We identified a histone H3.3 sub-variant, H3mm7, to be specifically expressed in skeletal muscle satellite cells. H3mm7 knockout mice demonstrated an essential role of H3mm7 in skeletal muscle regeneration. Chromatin analysis revealed that H3mm7 facilitates transcription by forming an open chromatin structure around promoter regions including those of myogenic genes.
Project description:Analysis of Beat AML sequencing data revealed a recurrent frameshift variant (R939Pfs*Ter36) in Zinc Finger 687 (ZNF687) that was observed in ~1% of patients and has not been previously described. ZNF687 encodes a transcription factor containing DNA binding C2H2 zinc finger and has been studied in select other malignancies, including Paget’s disease of bone that is associated with giant cell tumor (PDB/GCT) and hepatocellular carcinoma. It is part of a network with ZMYND8 and two additional zinc finger proteins, ZNF592 and ZNF532, that associate with H3K4 demethylation machinery and regulates gene transcription. The R939Pfs*Ter36 frameshift induced overexpression of ZNF687 compared with wild-type, and the overexpressed protein was mislocalized to the cytoplasm. We further performed RNA sequencing on HEK293 cells expressing the frameshift variant, wild-type, or a previously identified variant (P937R) that has been reported as a germline ZNF687 variant characterized to predispose to PDB/GCT. We observed the R939Pfs*Ter36 frameshift to induce activation of oxidative phosphorylation, inactivation of histone methylation machinery, and significant downregulation of lysine methyltransferase 2D (KMT2D) compared with wild-type and P937R. Overall, these findings suggest that ZNF687 R939Pfs*Ter36 plays an important role in AML pathogenesis, which could aid in diagnostic precision, and may impact therapeutic responses.
Project description:In this study, we recruited a patient with Hereditary spherocytosis (HS) detected to have a novel heterozygous variant in the SPTB in the proband. Sanger sequencing of variant alleles and haplotype linkage analysis were performed simultaneously. Five embryos were identified with one heterozygous and four not carrying the SPTB variant. Single-cell amplification and whole genome sequencing showed that three embryos had varying degrees of trisomy mosaicism.
Project description:Probing the rice genome for novel histone coding genes revealed a genera specific, histone H4 variant with several variations in N-terminal tail sequence motifs, expressing in a tissue-specific manner. Genetic perturbation of the H4 variant in rice led to defects in growth and fertility. Probing the chromatin binding sites of the H4 variant with a custom antibody revealed its binding at specific genes and its knockout led to mis-expression of stress-associated genes. Stress-challenged plants showed loss of the H4 variant and re-distribution of other H4 linked histone marks. In vitro reconstituted rice nucleosomes with H4 variant histones displayed atypical properties in terms of stability, intra-nucleosome binding and structure, when compared to the canonical nucleosomes.
Project description:Probing the rice genome for novel histone coding genes revealed a genera specific, histone H4 variant with several variations in N-terminal tail sequence motifs, expressing in a tissue-specific manner. Genetic perturbation of the H4 variant in rice led to defects in growth and fertility. Probing the chromatin binding sites of the H4 variant with a custom antibody revealed its binding at specific genes and its knockout led to mis-expression of stress-associated genes. Stress-challenged plants showed loss of the H4 variant and re-distribution of other H4 linked histone marks. In vitro reconstituted rice nucleosomes with H4 variant histones displayed atypical properties in terms of stability, intra-nucleosome binding and structure, when compared to the canonical nucleosomes.
Project description:Probing the rice genome for novel histone coding genes revealed a genera specific, histone H4 variant with several variations in N-terminal tail sequence motifs, expressing in a tissue-specific manner. Genetic perturbation of the H4 variant in rice led to defects in growth and fertility. Probing the chromatin binding sites of the H4 variant with a custom antibody revealed its binding at specific genes and its knockout led to mis-expression of stress-associated genes. Stress-challenged plants showed loss of the H4 variant and re-distribution of other H4 linked histone marks. In vitro reconstituted rice nucleosomes with H4 variant histones displayed atypical properties in terms of stability, intra-nucleosome binding and structure, when compared to the canonical nucleosomes.
Project description:In a meta-analysis of three GWASs in the Japanese population, we identified a novel locus at 16p12.3 significantly associated with pancreatic cancer susceptibility. A series of experiments were performed to explore the functional impact of the nonsynonymous lead SNP rs78193826 of the GP2 gene at 16p12.3 on global gene expression. Based on CRISPR-Cas9-induced mutation, RNA-seq, and GSEA analyses, we demonstrated that the functional relevance of rs78193826 may involve modulation of KRAS activity.
Project description:We use stable expression of a cystathionine-beta synthase (CBS) variant library in HEK293T cells to identify CBS coding sequence variants that alter mRNA abundance
Project description:Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis