Expansion of stochastic expression repertoire by tandem duplication in mouse Protocadherin-α cluster
نویسندگان
چکیده
Tandem duplications are concentrated within the Pcdh cluster throughout vertebrate evolution and as copy number variations (CNVs) in human populations, but the effects of tandem duplication in the Pcdh cluster remain elusive. To investigate the effects of tandem duplication in the Pcdh cluster, here we generated and analyzed a new line of the Pcdh cluster mutant mice. In the mutant allele, a 218-kb region containing the Pcdh-α2 to Pcdh-αc2 variable exons with their promoters was duplicated and the individual duplicated Pcdh isoforms can be disctinguished. The individual duplicated Pcdh-α isoforms showed diverse expression level with stochastic expression manner, even though those have an identical promoter sequence. Interestingly, the 5'-located duplicated Pcdh-αc2, which is constitutively expressed in the wild-type brain, shifted to stochastic expression accompanied by increased DNA methylation. These results demonstrate that tandem duplication in the Pcdh cluster expands the stochastic expression repertoire irrespective of sequence divergence.
منابع مشابه
Identification and Comparative Analysis of the Protocadherin Cluster in a Reptile, the Green Anole Lizard
BACKGROUND The vertebrate protocadherins are a subfamily of cell adhesion molecules that are predominantly expressed in the nervous system and are believed to play an important role in establishing the complex neural network during animal development. Genes encoding these molecules are organized into a cluster in the genome. Comparative analysis of the protocadherin subcluster organization and ...
متن کاملComparative DNA sequence analysis of mouse and human protocadherin gene clusters.
The genomic organization of the human protocadherin alpha, beta, and gamma gene clusters (designated Pcdh alpha [gene symbol PCDHA], Pcdh beta [PCDHB], and Pcdh gamma [PCDHG]) is remarkably similar to that of immunoglobulin and T-cell receptor genes. The extracellular and transmembrane domains of each protocadherin protein are encoded by an unusually large "variable" region exon, while the intr...
متن کاملCTCF and cohesin help neurons raise their self-awareness.
I n the brain neurons form extensively intermingled projections and synaptic interactions between them. To achieve proper neural connectivity, interactions between sections belonging to the same neuron are avoided. However, how can a cell tell, when it encounters another neuronal projection, whether it is part of the same cell? In other words, how do neurons become self-aware? Work of the last ...
متن کاملEffects of co-administration of ghrelin agonist (GHRP-2) and GH on TNF-α, IL-6 and iNOS gene expression induced by LPS in the mouse brain
The aim of this study was to examine the anti-inflammatory effects of co-administration of growthhormone-releasing peptide-2 (GHRP-2) and growth hormone (GH) on tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) gene expression induced by LPS in the mousebrain. Thirty-five male NMRI mice (25±5 g) were injected through the mouse tail vein with saline,...
متن کاملRegulation of protocadherin gene expression by multiple neuron-restrictive silencer elements scattered in the gene cluster
The clustered protocadherins are a subfamily of neuronal cell adhesion molecules that play an important role in development of the nervous systems in vertebrates. The clustered protocadherin genes exhibit complex expression patterns in the central nervous system. In this study, we have investigated the molecular mechanism underlying neuronal expression of protocadherin genes using the protocadh...
متن کامل