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Huanming Yang

Publications and source records attributed to Huanming Yang.

3 recordsLinked to original sources

Evolution trajectories of snake genes and genomes revealed by comparative analyses of five-pacer viper

Snakes numerous fascinating features distinctive from other tetrapods necessitate a rich history of genome evolution that is still obscure. To address this, we report the first high-quality genome of a viper, Deinagkistrodon acutus and comparative analyses using other species from major snake and lizard lineages. We map the evolution trajectories of transposable elements (TEs), developmental genes and sex chromosomes onto the snake phylogeny. TEs exhibit dynamic lineage-specific expansion. And in the viper many TEs may have been rewired into the regulatory network of brain genes, as shown by their associated expression with nearby genes in the brain but not in other tissues. We detect signatures of adaptive evolution in olfactory, venom and thermal-sensing genes, and also functional degeneration of genes associated with vision and hearing. Many Hox and Tbx limb-patterning genes show evidence of relaxed selective constraints, and such genes phylogenetic distribution supports fossil evidence for a successive loss of forelimbs then hindlimbs during the snake evolution. Finally, we infer that the Z and W sex chromosomes had undergone at least three recombination suppression events at the ancestor of advanced snakes, with the W chromosomes showing a gradient of degeneration from basal to advanced snakes. These results, together with all the genes identified as undergoing adaptive or degenerative evolution episodes at respective snake lineages forge a framework for our deep understanding into snakes molecular evolution history.

Evolutionary Biology

TET1 Modulates H4K16 Acetylation by Interacting with hMOF to Regulate Expression of DNA Repair Genes and Oncogenic Transformation

The Ten Eleven Translocation 1 (TET1) protein is a DNA demethylase that regulates gene expression through alteration of DNA methylation. Recent studies have demonstrated that TET1 could modulate transcriptional expression independent of its DNA demethylation activity; however, the detailed mechanisms underlying TET1s role in such transcriptional regulation remain not well understood. Here, we uncovered that Tet1 formed a chromatin complex with histone acetyltransferase Mof and scaffold protein Sin3a in mouse embryonic stem cells by integrative genomic analysis using publicly available ChIP-seq data sets. Specifically, the TET1/SIN3A/hMOF complex mediates acetylation of histone H4 at lysine 16, via facilitating the binding of hMOF on chromatin, to regulate expression of important DNA repair genes in DNA double strand breaks, including TP53BP1, RAD50, RAD51, and BRCA1, for homologous recombination and non-homologous end joining repairs. Under hydrogen peroxide-induced DNA damage, dissociation of TET1 and hMOF from chromatin, concurrent with increased binding of SIRT1 on chromatin, led to hypo-acetylation of H4K16, reduced expression of these DNA repair genes, and DNA repair defects in a DNA methylation independent manner. A similar epigenetic dynamic alteration was also observed in H-RASV12 oncogenic-transformed cells, supporting the notion that suppression of TET1 downregulates DNA repair genes through modifying H4K16ac, instead of its demethylation function, and therefore contribute to tumorigenesis. Taken together, our results suggested a mechanistic link between a novel TET1 complex and H4K16ac, DNA repair genes expression, and genomic instability.

Molecular Biology

A Complete Public Domain Family Genomics Dataset

BackgroundThe availability of open access genomic data is essential for the personal genomics field. Public genomic data allow comparative analyses, testing of new tools and genotype-phenotype association studies. Personal genomics data of unrelated individuals are available in the public domain, notably the Personal Genome Project; however, to date genomics family data and metadata are severely lacking, mainly due to cost, privacy concerns or restricted access to Next Generation Sequencing (NGS) technology. Family data have a lot to offer as they allow the study of heritability, something which is impossible to do just by using unrelated individuals.\n\nFindingsA whole family from Southern Spain decided to genotype, sequence and analyse their personal genomes making them publicly available under a Creative Commons 0 license (CC0; commonly denominated as public domain). These data include a) five 23andMe SNP chip genotype bed files, b) four raw exomes with their assorted bam files and VCF files, c) a metagenomic raw sequencing data file and d) derived data of likely phenotypes using SNPedia-derived tools.\n\nConclusionsTo our knowledge this is the first CC0 released set of genomic, phenotypic and metagenomic data for a whole family. This dataset is also unique in that it was obtained through direct-to-consumer genetic tests. Hence any ordinary citizen with enough budget and samples should be able to reproduce this experiment. We envisage this dataset to be a useful resource for a variety of applications in the personal genomics field as a) negative control data for trait association discovery, b) testing data for development of new software and c) sample data for heritability studies. We encourage prospective users to share with us derived results so that they can be added to our existing collection.

Genomics