Biology subjects

Shen, Z.

Publications and source records attributed to Shen, Z..

131 records · Page 8Linked to original sources

bioRxiv2019

Existence and functions of hypothalamic kisspeptin neuropeptide signaling system in a non-chordate deuterostome species

The kisspeptin (Kp) system is a central modulator of the hypothalamic-pituitary-gonadal axis in vertebrates. Its existence outside the vertebrate lineage remains largely unknown. Here we report the identification and characterization of Kp system in the sea cucumber Apostichopus japonicus. The gene encoding the Kp precursor, generates two mature neuropeptides, AjKiss1a and AjKiss1b. The Kp receptors, AjKissR1 and AjKissR2, are strongly activated by synthetic A. japonicus and vertebrate Kps, triggering a rapid intracellular mobilization of Ca2+, followed by receptor internalization. AjKissR1 and AjKissR2 share similar intracellular signaling pathways via Gq/PLC/PKC/MAPK cascade, when activated by C-terminal decapeptide (AjKiss1b-10). The A. japonicus Kp system functions in mutiple tissues which are closely related to reproduction and metabolism. Overall, our findings uncover for the first time, to our knowledge, the existence and function of the Kp system in a non-chordate species and provide new evidence to support the ancient origin of the hypothalamic neurosecretory system.

evolutionary biology↗

bioRxiv2019

Cell type-specific enhancer-promoter connectivity maps in the human brain and disease risk association

Unique cell type-specific patterns of activated enhancers can be leveraged to interpret non-coding genetic variation associated with complex traits and diseases such as neurological and psychiatric disorders. Here, we have defined active promoters and enhancers for major cell types of the human brain. Whereas psychiatric disorders were primarily associated with regulatory regions in neurons, idiopathic Alzheimers disease (AD) variants were largely confined to microglia enhancers. Interactome maps connecting GWAS variants in cell type-specific enhancers to gene promoters revealed an extended microglia gene network in AD. Deletion of a microglia-specific enhancer harboring AD-risk variants ablated BIN1 expression in microglia but not in neurons or astrocytes. These findings revise and expand the genes likely to be influenced by non-coding variants in AD and suggest the probable brain cell types in which they function.\n\nOne Sentence SummaryIdentification of cell type-specific regulatory elements in the human brain enables interpretation of non-coding GWAS risk variants.

neuroscience↗

bioRxiv2019

Dynamic regulation of immunity through post-translational control of defense transcript splicing

Survival of all living organisms requires the ability to detect attack and swiftly counter with protective immune responses. Despite considerable mechanistic advances, interconnectivity of signaling circuits often remains unclear. A newly-characterized protein, IMMUNOREGULATORY RNA-BINDING PROTEIN (IRR), negatively regulates immune responses in both maize and Arabidopsis, with disrupted function resulting in enhanced disease resistance. IRR physically interacts with, and promotes canonical splicing of, transcripts encoding defense signaling proteins, including the key negative regulator of pattern recognition receptor signaling complexes, CALCIUM-DEPENDENT PROTEIN KINASE 28 (CPK28). Upon immune activation by Plant Elicitor Peptides (Peps), IRR is dephosphorylated, disrupting interaction with CPK28 transcripts and resulting in accumulation of an alternative splice variant encoding a truncated CPK28 protein with impaired kinase activity and diminished function as a negative regulator. We demonstrate a novel circuit linking Pep-induced post-translational modification of IRR with post-transcriptionally-mediated attenuation of CPK28 function to dynamically amplify Pep signaling and immune output.\n\nOne Sentence SummaryPlant innate immunity is promoted by post-translational modification of a novel RNA-binding protein that regulates alternative splicing of transcripts encoding defense signaling proteins to dynamically increase immune receptor signaling capacity through deactivation of a key signal-buffering circuit.

plant biology↗

bioRxiv2018

Diverse motif ensembles specify non-redundant DNA binding activities of AP-1 family members in macrophages

Mechanisms by which members of the AP-1 family of transcription factors play both redundant and non-redundant biological roles despite recognizing the same DNA sequence remain poorly understood. To address this question, we investigated the molecular functions and genome-wide DNA binding patterns of AP-1 family members in macrophages. ChIP-sequencing showed overlapping and distinct binding profiles for each factor that were remodeled following TLR4 ligation. Development of a machine learning approach that jointly weighs hundreds of DNA recognition elements yielded dozens of motifs predicted to drive factor-specific binding profiles. Machine learning-based predictions were confirmed by analysis of the effects of mutations in genetically diverse mice and by loss of function experiments. These findings provide evidence that non-redundant genomic locations of different AP-1 family members in macrophages largely result from collaborative interactions with diverse, locus-specific ensembles of transcription factors and suggest a general mechanism for encoding functional specificities of their common recognition motif.

genomics↗

bioRxiv2017

Quantitative proteomic analysis of auxin signaling during seedling development

Auxin induces rapid gene expression changes throughout plant development. How these transcriptional responses relate to changes in protein abundance is not well characterized. We have identified auxin regulated proteins in whole seedlings, roots and hypocotyls and at three different time points (30 min, 120 min and 3 hours) using an iTRAQ (isobaric tags for relative and absolute quantification) based quantitative proteomics approach. These profiling experiments detected 4,701 proteins from seedling tissue, 6,740 proteins from root tissue and 3,925 proteins from hypocotyl tissue. Comparisons between the differentially expressed proteins data sets showed little overlap, suggesting that auxin proteomes exhibit both temporal and spatial specificity. Numerous proteins showed significant changes in abundance following auxin treatment independent of changes in cognate transcript abundance. This includes several well characterized proteins with various roles in auxin pathways, suggesting that complex gene regulation mechanisms follow auxin signaling events. Specifically, regulation of translation may play a role as inferred from MapMan categorization analyses and protein interaction networks comprised of auxin regulated proteins. Additionally, functional categorization of auxin regulated proteins indicates rapid and complex metabolic changes occur in both roots and hypocotyls in response to auxin which are not apparent from transcriptome analyses. Altogether these data describe novel auxin-regulated proteomes and are an excellent resource for identifying new downstream signaling components related to auxin-mediated plant growth and development.

plant biology↗