One neuron–one receptor rule in the mouse olfactory system

Serizawa, Shou; Miyamichi, Kazunari; Sakano, Hitoshi

doi:10.1016/j.tig.2004.09.006

Cited by 214 publications

(168 citation statements)

References 56 publications

Supporting

Mentioning

161

Contrasting

Unclassified

Order By: Relevance

“…The stagespecific control of VSG gene expression implies that the IP pathway may also participate in the control and coordination of stage-specific processes during the life cycle in African trypanosomes. In addition, the IP pathway is conserved from yeast to humans (18); hence, the IP pathway may function in telomeric silencing and allelic exclusion in other organisms such as the expression of var genes in Plasmodium spp., or perhaps in the allelic exclusion of odorant receptors in mammals (40,41). T. cruzi and Leishmania, which are related to T. brucei, conserve the IP pathway but lack telomeric ESs and may have adapted the pathway for alternate functions, e.g., control the expression of numerous surface proteins.…”

Section: Discussionmentioning

confidence: 99%

Inositol phosphate pathway controls transcription of telomeric expression sites in trypanosomes

Cestari

Stuart

2015

Proc. Natl. Acad. Sci. U.S.A.

143

View full text Add to dashboard Cite

African trypanosomes evade clearance by host antibodies by periodically changing their variant surface glycoprotein (VSG) coat. They transcribe only one VSG gene at a time from 1 of about 20 telomeric expression sites (ESs). They undergo antigenic variation by switching transcription between telomeric ESs or by recombination of the VSG gene expressed. We show that the inositol phosphate (IP) pathway controls transcription of telomeric ESs and VSG antigenic switching in Trypanosoma brucei. Conditional knockdown of phosphatidylinositol 5-kinase (TbPIP5K) or phosphatidylinositol 5-phosphatase (TbPIP5-Pase) or overexpression of phospholipase C (TbPLC) derepresses numerous silent ESs in T. brucei bloodstream forms. The derepression is specific to telomeric ESs, and it coincides with an increase in the number of colocalizing telomeric and RNA polymerase I foci in the nucleus. Monoallelic VSG transcription resumes after reexpression of TbPIP5K; however, most of the resultant cells switched the VSG gene expressed. TbPIP5K, TbPLC, their substrates, and products localize to the plasma membrane, whereas TbPIP5Pase localizes to the nucleus proximal to telomeres. TbPIP5Pase associates with repressor/activator protein 1 (TbRAP1), and their telomeric silencing function is altered by TbPIP5K knockdown. These results show that specific steps in the IP pathway control ES transcription and antigenic switching in T. brucei by epigenetic regulation of telomere silencing.O nly one of the ∼20 telomeric expression sites (ESs) is transcribed at a time in Trypanosoma brucei in the mammalian infectious stage bloodstream (BF) or metacyclic forms (MFs), whereas no ES is transcribed in the insect stage procyclic forms (PFs) (1). Each ES contains 1 telomeric variant surface glycoprotein (VSG) gene, whose expression confers a distinct cellular antigenic type and up to 12 expression site-associated genes (ESAGs) whose functions are incompletely understood ( Fig. 1A) (2-4). The parasites evade immune clearance by periodically changing antigenic type by switching transcription between ESs or by ES recombination with the ∼2,500 non-ES VSG genes and pseudogenes (5, 6). ESs are transcribed by RNA polymerase I (Pol I), which initiates at the single promoter at all ESs but terminates within a few kilobases except at one fully transcribed ES (7,8).RNAi knockdown of expression of the nuclear protein TbRAP1 that interacts with the TTAGGG-binding factor (TbTRF) or of the nuclear lamina protein 1 (TbNUP1) or deletion of the histonelysine N-methyltransferase DOT1B (TbDOT1B) alleles each results in transcription of silent ESs (9-11). Similarly, RNAi knockdown of the transcription facilitating histone chaperone suppressor of ty 16 (TbSPT16) or the SWI2/SNF2-related chromatin-remodeling protein TbISWI or deletion of histone deacetylase sirtuin 2-related protein 1 (TbSIR2RP1) each increases transcription near the promoter but not the VSG gene of silent . These results indicate that the control of ES transcription involves telomeric silencing (15), which entails...

show abstract

Section: Discussionmentioning

confidence: 99%

Inositol phosphate pathway controls transcription of telomeric expression sites in trypanosomes

Cestari

Stuart

2015

Proc. Natl. Acad. Sci. U.S.A.

143

View full text Add to dashboard Cite

show abstract

“…However, if the expression areas of various ORs are arranged in a continuous and overlapping manner, we may have to consider a different mechanism, one that detects a gradient or a relative location in the OE for each OR gene along the dorsomedial/ventrolateral axis. If this is the case, the choice of the OR genes may be more restricted by the location of the OSN in the OE than what has been thought (Serizawa et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Continuous and Overlapping Expression Domains of Odorant Receptor Genes in the Olfactory Epithelium Determine the Dorsal/Ventral Positioning of Glomeruli in the Olfactory Bulb

Miyamichi¹,

Serizawa²,

Kimura³

et al. 2005

J. Neurosci.

277

327

View full text Add to dashboard Cite

In mammals, olfactory signals received by odorant receptors (ORs) in the olfactory epithelium (OE) are converted to a topographical map of activated glomeruli in the olfactory bulb (OB). It has been reported that the OE can be divided into four topographically distinct zones and that olfactory sensory neurons (OSNs) expressing a particular OR gene are randomly distributed within one zone. Here, we analyzed 80 different class II OR genes for their expression patterns in the OE by in situ hybridization. It was found that the expression area in the OE does not always fit into one of the four conventional zones. Expression areas are specific to each OR gene and are arranged in an overlapping and continuous manner in the OE. We also analyzed a spatial relationship between the OE and the OB for OSN projection. Our transgenic as well as DiI retrograde staining experiments demonstrated that the dorsal/ventral arrangement of glomeruli in the OB is correlated with the expression areas of corresponding ORs along the dorsomedial/ventrolateral axis in the OE. The present study indicates that the OR gene choice may be more restricted by the OSN location in the OE than what has been thought.

show abstract

“…These results indicated that the H region is a cis-acting locus control region (LCR)/enhancer that activates the MOR28 cluster, at least in the transgenic construct. Like other LCRs in the globin gene and the photopigment gene systems in the human (14,15), we have postulated that a chromatinremodeling complex assembled at H activates one OR gene at a time, by physical association with one promoter site (16).…”

mentioning

confidence: 90%

Deletion of the core- H region in mice abolishes the expression of three proximal odorant receptor genes in cis

Nishizumi

Inoue

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

107

118

View full text Add to dashboard Cite

We have previously reported that a 2.1-kb homology (H) sequence, conserved between mouse and human, regulates the odorant receptor (OR) gene MOR28 in transgenic mice. Here, we narrowed down the essential sequences of the H to a core of 124 bp by using a transient expression system in zebrafish embryos. Transgenic experiments in mice demonstrated that the core-H sequence is sufficient to endow expression of the MOR28 minigene. Deletion and mutation analyses of the core-H region revealed two homeodomain sequences to be essential for the H enhancer activity. Targeted deletion of the core-H abolished expression of three proximal OR genes, MOR28, MOR10, and MOR83, in cis, indicating the presence of another locus control region/enhancer in the downstream region, that regulates four distal OR genes in the same MOR28 cluster. In the heterozygous mice, the H ؊ phenotype of the mutant allele was not rescued by the wild-type H ؉ allele in trans.olfactory sensory neuron ͉ gene targeting ͉ locus control region ͉ transgenic mouse ͉ zebrafish

show abstract

One neuron–one receptor rule in the mouse olfactory system

Cited by 214 publications

References 56 publications

Inositol phosphate pathway controls transcription of telomeric expression sites in trypanosomes

Inositol phosphate pathway controls transcription of telomeric expression sites in trypanosomes

Continuous and Overlapping Expression Domains of Odorant Receptor Genes in the Olfactory Epithelium Determine the Dorsal/Ventral Positioning of Glomeruli in the Olfactory Bulb

Deletion of the core- H region in mice abolishes the expression of three proximal odorant receptor genes in cis

Contact Info

Product

Resources

About