Structural insights into the recognition of histone H3Q5 serotonylation by WDR5

Serotonylation of histone H3Q5 (H3Q5ser) is a recently identified posttranslational modification of histones that acts as a permissive marker for gene activation in synergy with H3K4me3 during neuronal cell differentiation. However, any proteins that specifically recognize H3Q5ser remain unknown. Here, we found that WDR5 interacts with the N-terminal tail of histone H3 and functions as a “reader” for H3Q5ser. Crystal structures of WDR5 in complex with H3Q5ser and H3K4me3Q5ser peptides revealed that the serotonyl group is accommodated in a shallow surface pocket of WDR5. Experiments in neuroblastoma cells demonstrate that H3K4me3 modification is hampered upon disruption of WDR5-H3Q5ser interaction. WDR5 colocalizes with H3Q5ser in the promoter regions of cancer-promoting genes in neuroblastoma cells, where it promotes gene transcription to induce cell proliferation. Thus, beyond revealing a previously unknown mechanism through which WDR5 reads H3Q5ser to activate transcription, our study suggests that this WDR5-H3Q5ser–mediated epigenetic regulation apparently promotes tumorigenesis.

Expression of zebrafish Brn1.2 (Pou3f2) and two Brn-3a (Pou4f1) POU genes in brain and sensory structures

POU genes are characterized by a conserved POU DNA-binding domain, and are divided into six subclasses. Class III and IV POU genes are predominantly expressed in the developing nervous system. POU class III genes are critical for several neuronal cell differentiation and class IV POU genes serve important functions in the differentiation and survival of sensory neurons. In this study, we attempted to identify POU genes in the zebrafish and pufferfish genomes by using existing bioinformatics tools. We analysed the expression of zebrafish brn1.2 and brn3a genes (brn3a1 and brn3a2)) using whole-mount in situ hybridisation. Similarly to the mammalian orthologue, zebrafish brn1.2 was widely expressed in the forebrain, midbrain and hindbrain. During the late stages of embryogenesis, brn1.2 expressing cells were located in the preoptic area and in the auditory vesicles. Expression of both zebrafish brn3a genes was detected in trigeminal ganglia, cranial sensory ganglia, sensory neurons along the dorsal spinal cord, in the anterior and posterior lateral line placodes (ALL and PLL), retinal ganglion cell layer, optic tectum and in small cell clusters in the forebrain and hindbrain. Similar to mammalian Brn3a, zebrafish brn3a genes were detected in the retina and sensory structures. However, different domains of expression were also observed, namely in spinal sensory neurons, and lateral line system.

Para-substituted sulfonic acid-doped protonated emeraldine salt nanobuds: a potent neural interface targeting PC12 cell interactions and promotes neuronal cell differentiation

Surface functionalized protonated emeraldine salt (PES) synthesized at 0.18 V provide robust electrically conductive system with low surface resistivity (81.18 mΩ). The PES show ability of cell-type specific microenvironment supporting PC12 cells for neural differentiation.

Structural insights into the recognition of histone H3Q5 serotonylation by WDR5

Serotonylation of histone H3Q5 (H3Q5ser) is a recently identified posttranslational modification of histones that apparently acts as a permissive marker for gene activation in synergy with H3K4me3 during neuronal cell differentiation. However, any proteins which specifically recognize H3Q5ser remain unknown. Here, we discovered that WDR5 interacts with the N-terminal tail of histone H3 and functions as a ‘reader’ for H3Q5ser. Crystal structures of WDR5 in complex with H3Q5ser and H3K4me3Q5ser peptides revealed that the serotonyl group is accommodated in a shallow surface pocket of WDR5. Experiments in neuroblastoma cells demonstrate that WDR5 colocalizes with H3Q5ser in the promoter regions of cancer-promoting genes, where it promotes gene transcription to induce cell proliferation. Thus, beyond revealing a previously unknown mechanism through which WDR5 reads H3Q5ser to activate transcription, our study suggests that this WDR5-H3Q5ser mediated epigenetic regulation apparently promotes tumorigenesis.

Evaluation of PC12 Cell Neural Differentiation on Graphene Coated ITO Microchips

In this study, the impact of graphene on neuronal differentiation of PC12 cells into neuron-like cells was evaluated in conjunction with electrical stimuli. First, an ITO (Indium Tin Oxide) microchip with a certain number of electrodes was fabricated using photolithography and then a chemically synthesized graphene was coated on the microchip. The electrical stimulation was applied through the ITO-microchip. Following optimization of neuronal differentiation conditions, the effect of AC and DC electrical stimulation on both bare and graphene-coated ITO-microchips for neuronal differentiation was investigated. According to the results, it was observed that electrical stimulation with direct current for 30 minutes caused a large degree of neuronal cell differentiation on the graphene coated ITO-microchips. The results were also verified by real-time qPCR.

Evaluation of PC12 Cell Neural Differentiation on Graphene Coated ITO Microchips

In this study, the impact of graphene on neuronal differentiation of PC12 cells into neuron-like cells was evaluated in conjunction with electrical stimuli. First, an ITO (Indium Tin Oxide) microchip with a certain number of electrodes was fabricated using photolithography and then a chemically synthesized graphene was coated on the microchip. The electrical stimulation was applied through the ITO-microchip. Following optimization of neuronal differentiation conditions, the effect of AC and DC electrical stimulation on both bare and graphene-coated ITO-microchips for neuronal differentiation was investigated. According to the results, it was observed that electrical stimulation with direct current for 30 minutes caused a large degree of neuronal cell differentiation on the graphene coated ITO-microchips. The results were also verified by real-time qPCR.