JMJD1B, a novel player in histone H3 and H4 processing to ensure genome stability.

Background: Maintaining a proper supply of soluble histones throughout the cell cycle is important to ensure chromatin and genome stability. Following their synthesis, histones undergo a series of maturation steps to prepare them for deposition onto chromatin.

Results: Here, we identify the lysine demethylase JMJD1B as a novel player in the maturation cascade that contributes to regulate histone provision.

PP32 and SET/TAF-Iβ proteins regulate the acetylation of newly synthesized histone H4.

Newly synthesized histones H3 and H4 undergo a cascade of maturation steps to achieve proper folding and to establish post-translational modifications prior to chromatin deposition. Acetylation of H4 on lysines 5 and 12 by the HAT1 acetyltransferase is observed late in the histone maturation cascade. A key question is to understand how to establish and regulate the distinct timing of sequential modifications and their biological significance.

The CENP-T/-W complex is a binding partner of the histone chaperone FACT.

The CENP-T/-W histone fold complex, as an integral part of the inner kinetochore, is essential for building a proper kinetochore at the centromere in order to direct chromosome segregation during mitosis. Notably, CENP-T/-W is not inherited at centromeres, and new deposition is absolutely required at each cell cycle for kinetochore function. However, the mechanisms underlying this new deposition of CENP-T/-W at centromeres are unclear.

The histone chaperone HJURP is a new independent prognostic marker for luminal A breast carcinoma.

Background: Breast cancer is a heterogeneous disease with different molecular subtypes that have varying responses to therapy. An ongoing challenge in breast cancer research is to distinguish high-risk patients from good prognosis patients. This is particularly difficult in the low-grade, ER-positive luminal A tumors, where robust diagnostic tools to aid clinical treatment decisions are lacking.

The histone variant composition of centromeres is controlled by the pericentric heterochromatin state during the cell cycle.

Correct chromosome segregation requires a unique chromatin environment at centromeres and in their vicinity. Here, we address how the deposition of canonical H2A and H2A.Z histone variants is controlled at pericentric heterochromatin (PHC).

Dynamics of histone H3 deposition in vivo reveal a nucleosome gap-filling mechanism for H3.3 to maintain chromatin integrity.

Establishment of a proper chromatin landscape is central to genome function. Here, we explain H3 variant distribution by specific targeting and dynamics of deposition involving the CAF-1 and HIRA histone chaperones. Impairing replicative H3.

A specific function for the histone chaperone NASP to fine-tune a reservoir of soluble H3-H4 in the histone supply chain.

Proper genome packaging requires coordination of both DNA and histone metabolism. While histone gene transcription and RNA processing adequately provide for scheduled needs, how histone supply adjusts to unexpected changes in demand remains unknown. Here, we reveal that the histone chaperone nuclear autoantigenic sperm protein (NASP) protects a reservoir of soluble histones H3-H4.

Auditory outcomes after implantation and electrical stimulation of the lateral ampullar nerve in guinea pig.

Objective: To determine in a guinea pig model the factors of invasiveness of a bipolar electrode implanted in the horizontal semicircular canal (HSC) and to evaluate the consequences on hearing of electrical stimulation of the ampullary nerve.

Design: Sixteen guinea pigs divided into four groups underwent surgical opening of the HSC of one ear as follows: control (group 1), cyanoacrylate glue application on the HSC opening (group 2), electrode implantation with cyanoacrylate glue on the HSC opening (group 3), and electrode implantation with electrical stimulation (1 hr/day) for 9 days (group 4). Auditory brainstem responses were recorded before and after surgery and after electrical stimulation.

Xenopus HJURP and condensin II are required for CENP-A assembly.

Centromeric protein A (CENP-A) is the epigenetic mark of centromeres. CENP-A replenishment is necessary in each cell cycle to compensate for the dilution associated to DNA replication, but how this is achieved mechanistically is largely unknown. We have developed an assay using Xenopus egg extracts that can recapitulate the spatial and temporal specificity of CENP-A deposition observed in human cells, providing us with a robust in vitro system amenable to molecular dissection.

SUMOylation promotes de novo targeting of HP1α to pericentric heterochromatin.

HP1 enrichment at pericentric heterochromatin is considered important for centromere function. Although HP1 binding to H3K9me3 can explain its accumulation at pericentric heterochromatin, how it is initially targeted there remains unclear. Here, in mouse cells, we reveal the presence of long nuclear noncoding transcripts corresponding to major satellite repeats at the periphery of pericentric heterochromatin.

Functional organization of vestibular commissural connections in frog.

Central vestibular neurons receive substantial inputs from the contralateral labyrinth through inhibitory and excitatory brainstem commissural pathways. The functional organization of these pathways was studied by a multi-methodological approach in isolated frog whole brains. Retrogradely labeled vestibular commissural neurons were primarily located in the superior vestibular nucleus in rhombomeres 2/3 and the medial and descending vestibular nucleus in rhombomeres 5-7.

Stimulation by cochlear implant in unilaterally deaf rats reverses the decrease of inhibitory transmission in the inferior colliculus.

In the last decade, numerous studies have investigated synaptic transmission changes in various auditory nuclei after unilateral cochlear injury. However, few data are available concerning the potential effect of electrical stimulation of the deafferented auditory nerve on the inhibitory neurotransmission in these nuclei. We report here for the first time the effect of chronic electrical stimulation of the deafferented auditory nerve on alpha1 subunit of the glycinergic receptor (GlyRalpha1) and glutamic acid decarboxylase (GAD)67 expression in the central nucleus of inferior colliculus (CIC).

Behavioral effects of a deletion in Kcnn2, the gene encoding the SK2 subunit of small-conductance Ca2+-activated K+ channels.

Small-conductance Ca(2+)-activated potassium (SK) channels are heteromeric complexes of SK alpha-subunits and calmodulin that modulate membrane excitability, are responsible for part of the after-hyperpolarization (AHP) following action potentials, and thus control the firing patterns and excitability of most central neurons. An engineered knockout allele for the SK2 subunit has previously been reported. The hippocampal neurons of these mice lacked the medium latency component of the AHP, but the animals were not described as presenting any overt behavioral phenotype.

Amino acid transporter (VIAAT, VGLUT2) and chloride cotransporter (KCC1, KCC2 and NKCC1) expression in the vestibular nuclei of intact and labyrinthectomized rat.

We report the first investigation of whether unilateral labyrinthectomy in adult rats affects the expression of two amino acid transporters, vesicular glutamate transporter 2 (VGLUT2) and vesicular inhibitory amino acid transporter (VIAAT) and of chloride cotransporters (KCC1, KCC2 and NKCC1) in the intact and deafferented medial vestibular nuclei (MVN). In situ hybridization with specific radioactive oligonucleotide probes and immunofluorescent methods were used in normal and unilaterally labyrinthectomized rats at various times following the lesion: 5 h, and 1, 3 and 8 days. In normal animals, several brainstem regions including the lateral, medial, superior and inferior vestibular nuclei contained VGLUT2, VIAAT and KCC2 mRNA.

Differential intrinsic response dynamics determine synaptic signal processing in frog vestibular neurons.

Central vestibular neurons process head movement-related sensory signals over a wide dynamic range. In the isolated frog whole brain, second-order vestibular neurons were identified by monosynaptic responses after electrical stimulation of individual semicircular canal nerve branches. Neurons were classified as tonic or phasic vestibular neurons based on their different discharge patterns in response to positive current steps.

Modulation of GABA receptor subunits in rat facial motoneurons after axotomy.

Facial nerve axotomy is a good model for studying neuronal plasticity and regeneration in the peripheral nervous system. In the present study, we investigated the effect of axotomy on the different subunits of GABA(A) and GABA(B) receptors of facial motoneurons. The facial nerve trunk was unilaterally sectioned and operated rats were sacrificed at 1, 3, 8, 30, and 60 days later.

Modulation of glycine receptor subunits and gephyrin expression in the rat facial nucleus after axotomy.

In the last decade, numerous studies have investigated molecular changes in excitatory glutamatergic receptors in axotomized motoneurons, but few data are available concerning the modulation of inhibitory amino acid receptors. We report here the effect of axotomy on the expression of glycine receptors, gephyrin, vesicular inhibitory amino acid transporter (VIAAT) and synapsin I in rat facial motor neurons as demonstrated by in situ hybridization and immunohistochemistry. The facial nerve trunk was sectioned unilaterally and rats were killed 1, 3, 8, 30 or 60 days after surgery.

An in situ hybridization and immunofluorescence study of GABA(A) and GABA(B) receptors in the vestibular nuclei of the intact and unilaterally labyrinthectomized rat.

We investigated whether the production of the sixteen subunits of the GABA(A) receptors and of the different variants of GABA Breceptors are modulated in rat medial vestibular nuclei (MVN) following unilateral labyrinthectomy. Specific alpha1-6, beta1-3, gamma1-3 and delta GABA(A) and GABA(B) B1 and B2receptor radioactive oligonucleotides were used for in situ hybridization to probe sections of rat vestibular nuclei. Specific antibodies against alpha1, beta2, beta3 and gamma2 subunits of GABA(A) receptors and against GABA( B)receptors were also used to detect a potential protein expression modulation.

An in situ hybridization and immunofluorescence study of glycinergic receptors and gephyrin in the vestibular nuclei of the intact and unilaterally labyrinthectomized rat.

We investigated whether the expression of glycinergic receptor (GLYR) subunits of gephyrin and of their mRNAs in the medial vestibular nuclei are affected following unilateral labyrinthectomy. Specific radioactive oligonucleotide probes recognizing the sequences encoding alpha1-3 and ss subunits of GLYR and the anchoring protein gephyrin were used to probe sections of vestibular nuclei. Signals in these in situ hybridization experiments were detected with film or by emulsion photography.