Biology subjects

Huang, N.

Publications and source records attributed to Huang, N..

8 recordsLinked to original sources

bioRxiv2018

Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3 HDAC complex

The CFP1 CXXC zinc finger protein targets the SET1/COMPASS complex to non-methylated CpG rich promoters to implement tri-methylation of histone H3 Ly4 (H3K4me3). Although H3K4me3 is widely associated with gene expression, the effects of CFP1 loss depend on chromatin context, so it is important to understand the relationship between CFP1 and other chromatin factors. Using a proteomics approach, we identified an unexpected link between C. elegans CFP-1 and a Rpd3/Sin3 histone deacetylase complex. We find that mutants of CFP-1, SIN-3, and the catalytic subunit SET-2/SET1 have similar phenotypes and misregulate common genes. CFP-1 directly binds SIN-3 through a region including the conserved PAH1 domain and recruits SIN-3 and the HDA-1/HDAC subunit to H3K4me3 enriched promoters. Our results reveal a novel role for CFP-1 in mediating interaction between SET1/COMPASS and a Sin3 HDAC complex at promoters and uncover coordinate regulation of gene expression by chromatin complexes having distinct activities.

genomics↗

bioRxiv2018

Neural underpinnnings of auditory salience in natural soundscapes

Salience is the mechanism whereby attention is automatically directed towards critical stimuli. Measuring the salience of a stimulus using behavioral methods risks confounds with top-down attention, particularly in the case of natural soundscapes. A distraction paradigm is employed here to measure physiological effects of salient auditory stimuli using electroencephalography. Several such effects are presented. In particular, a stimulus entrainment response is reduced by the presentation of distractor salient sounds. A reduction in oscillatory neural responses in the gamma frequency band is also observed following salient stimuli. These measures are used to identify salient portions of the natural scene. Finally, envelope decoding methods also indicate that salient stimuli attract attention away from other, task-related sounds.

neuroscience↗

bioRxiv2018

DeepSignal: detecting DNA methylation state from Nanopore sequencing reads using deep-learning

The Oxford Nanopore sequencing enables to directly detect methylation sites in DNA from reads without extra laboratory techniques. In this study, we develop DeepSignal, a deep learning method to detect DNA methylated sites from Nanopore sequencing reads. DeepSignal construct features from both raw electrical signals and signal sequences in Nanopore reads. Testing on Nanopore reads of pUC19, E. coli and human, we show that DeepSignal can achieve both higher read level and genome level accuracy on detecting 6mA and 5mC methylation comparing to previous HMM based methods. Moreover, DeepSignal achieves similar performance cross different methylation bases and different methylation motifs. Furthermore, DeepSignal can detect 5mC and 6mA methylation states of genome sites with above 90% genome level accuracy under just 5X coverage using controlled methylation data.

bioinformatics↗

bioRxiv2018

RNAs as proximity labeling media for identifying nuclear speckle positions relative to the genome

Nuclear speckles are interchromatin structures enriched in RNA splicing factors. Determining their relative positions with respect to the folded nuclear genome could provide critical information on co-and post-transcriptional regulation of gene expression. However, it remains challenging to identify which parts of the nuclear genome are in proximity to nuclear speckles, due to physical separation between nuclear speckle cores and chromatin. We hypothesized that noncoding RNAs including small nuclear RNAs, 7SK and Malat1, which accumulate at the periphery of nuclear speckles (nsaRNA, nuclear speckle associated RNA), may extend to sufficient proximity to the nuclear genome. Leveraging a transcriptome-genome interaction assay (MARGI), we identified nsaRNA-interacting genomic sequences, which exhibited clustering patterns (nsaPeaks) in the genome, suggesting existence of relatively stable interaction sites for nsaRNAs in nuclear genome. Posttranscriptional pre-mRNAs, which are known to be clustered to nuclear speckles, exhibited proximity to nsaPeaks but rarely to other genomic regions. Furthermore, CDK9 proteins that localize to the vicinity of nuclear speckles produced ChIP-seq peaks that overlapped with nsaPeaks. Our combined DNA FISH and immunofluorescence analysis in 182 single cells revealed a 3-fold increase in odds for nuclear speckles to localize near an nsaPeak than its neighboring genomic sequence. These data suggest a model that nsaRNAs locate in sufficient proximity to nuclear genome and leave identifiable genomic footprints, thus revealing the parts of genome proximal to nuclear speckles.

bioinformatics↗

bioRxiv2018

Chromatin accessibility dynamics across C. elegans development and ageing

An essential step for understanding the transcriptional circuits that control development and physiology is the global identification and characterization of regulatory elements. Here we present the first map of regulatory elements across the development and ageing of an animal, identifying 42,245 elements accessible in at least one C. elegans stage. Based on nuclear transcription profiles, we define 15,714 protein-coding promoters and 19,231 putative enhancers, and find that both types of element can drive orientation-independent transcription. Additionally, hundreds of promoters produce transcripts antisense to protein coding genes, suggesting involvement in a widespread regulatory mechanism. We find that the accessibility of most elements is regulated during development and/or ageing and that patterns of accessibility change are linked to specific developmental or physiological processes. The map and characterization of regulatory elements across C. elegans life provides a platform for understanding how transcription controls development and ageing.

genomics↗

bioRxiv2017

The complement system supports normal postnatal development and gonadal function in both sexes

Male and female infertility are clinically managed and classified as distinct diseases, and relatively little is known about mechanisms of gonadal function common to both sexes. We used genome-wide genetic analysis on 74,896 women and men to find rare genetic variants that modulate gonadal function in both sexes. This uncovered an association with variants disrupting CSMD1, a complement regulatory protein located on 8p23, in a genomic region with an exceptional evolution. We found that Csmd1 knockout mice display a diverse array of gonadal defects in both sexes, and in females, impaired mammary gland development that leads to increased offspring mortality. The complement pathway is significantly disrupted in Csmd1 mice, and further disruption of the complement pathway from joint inactivation of C3 leads to more extreme reproductive defects. Our results can explain a novel human genetic association with infertility and implicate the complement system in the normal development of postnatal tissues.

developmental biology↗

bioRxiv2017

A strain-specific multiplex RT-PCR for Australian rabbit haemorrhagic disease viruses uncovers a new recombinant virus variant in rabbits and hares

Rabbit haemorrhagic disease virus (RHDV, or GI.1), is a calicivirus in the genus Lagovirus that has been widely utilised in Australia as a biological control agent for the management of overabundant wild European rabbit (Oryctolagus cuniculus) populations since 1996. Recently, two exotic incursions of pathogenic lagoviruses have been reported in Australia; GI.1a-Aus, previously called RHDVa-Aus, is a GI.1a virus detected in January 2014, and the novel lagovirus GI.2 (previously known as RHDV2). Furthermore, an additional GI.1a strain, GI.1a-K5 (also known as 08Q712), was released nationwide in March 2017 as a supplementary tool for wild rabbit management. To discriminate between these lagoviruses, a highly sensitive strain-specific multiplex RT-PCR assay was developed, which allows fast, cost-effective, and sensitive detection of the four pathogenic lagoviruses currently known to be circulating in Australia. In addition, we developed a universal qRT-PCR assay to be used in conjunction with the multiplex assay that broadly detects all four viruses and facilitates quantification of viral RNA load in samples. These assays enable rapid detection, identification, and quantification of pathogenic lagoviruses in the Australian context. Using these assays, a novel recombinant lagovirus was detected in rabbit tissues samples, which contained the non-structural genes of GI.1a-Aus and the structural genes of GI.2. This variant was also recovered from the liver of a European brown hare (Lepus europaeus). The impact of this novel recombinant on Australian wild lagomorph populations and its competitiveness in relation to circulating field strains, particularly GI.2, requires further studies.

microbiology↗

bioRxiv2017

A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibiting cep-1/p53, endogenous meiotic double strand breaks, or the expression of MIRAGE1 DNA transposons. Functional redundancy among these factors and pathways underlies the importance of safeguarding the genome through multiple means.

genomics↗