Identification of the cluster control region for the protocadherin-beta genes located beyond the protocadherin-gamma cluster.
paper
Cited
Public
Unavailable
- Authors
- Yokota, Shinnichi; Hirayama, Teruyoshi; Hirano, Keizo; Kaneko, Ryosuke; Toyoda, Shunsuke; Kawamura, Yoshimi; Hirabayashi, Masumi; Hirabayashi, Takahiro; Yagi, Takeshi
- Year
- 2011
- Journal
- The Journal of biological chemistry
- PMID
- 21771796
- DOI
- 10.1074/jbc.M111.245605
- PMCID
- PMC3173131
The clustered protocadherins (Pcdhs), Pcdh-Ξ±, -Ξ², and -Ξ³, are transmembrane proteins constituting a subgroup of the cadherin superfamily. Each Pcdh cluster is arranged in tandem on the same chromosome. Each of the three Pcdh clusters shows stochastic and combinatorial expression in individual neurons, thus generating a hugely diverse set of possible cell surface molecules. Therefore, the clustered Pcdhs are candidates for determining neuronal molecular diversity. Here, we showed that the targeted deletion of DNase I hypersensitive (HS) site HS5-1, previously identified as a Pcdh-Ξ± regulatory element in vitro, affects especially the expression of specific Pcdh-Ξ± isoforms in vivo. We also identified a Pcdh-Ξ² cluster control region (CCR) containing six HS sites (HS16, 17, 17', 18, 19, and 20) downstream of the Pcdh-Ξ³ cluster. This CCR comprehensively activates the expression of the Pcdh-Ξ² gene cluster in cis, and its deletion dramatically decreases their expression levels. Deleting the CCR nonuniformly down-regulates some Pcdh-Ξ³ isoforms and does not affect Pcdh-Ξ± expression. Thus, the CCR effect extends beyond the 320-kb region containing the Pcdh-Ξ³ cluster to activate the upstream Pcdh-Ξ² genes. Thus, we concluded that the CCR is a highly specific regulatory unit for Pcdh-Ξ² expression on the clustered Pcdh genomic locus. These findings suggest that each Pcdh cluster is controlled by distinct regulatory elements that activate their expression and that the stochastic gene regulation of the clustered Pcdhs is controlled by the complex chromatin architecture of the clustered Pcdh locus.
No figures extracted from this document.
No chunks β full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
No citations found.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Protocadherin Ξ³C4 regulates neuronal survival and dendritic self-avoidance. | Higuchi R et al. | β | 2026 | β |
| CCCTC-binding factor N-terminal domain regulates clustered protocadherin gene expression by enhancing cohesin processivity. | Zhang Y et al. | β | 2025 | β |
| CRYΞ²B2 alters cell adhesion to promote invasion in a triple-negative breast cancer cell line. | Waly AA et al. | β | 2025 | β |
| Aberrant gene expression yet undiminished retinal ganglion cell genesis in iPSC-derived models of optic nerve hypoplasia. | Aparicio JG et al. | β | 2024 | β |
| Emergence and influence of sequence bias in evolutionarily malleable, mammalian tandem arrays. | Brovkina MV et al. | β | 2023 | β |
| Outward-oriented sites within clustered CTCF boundaries are key for intra-TAD chromatin interactions and gene regulation. | Ge X et al. | β | 2023 | β |
| WAPL functions as a rheostat of Protocadherin isoform diversity that controls neural wiring. | Kiefer L et al. | β | 2023 | β |
| Mouse models for the study of clustered protocadherins. | McLeod CM et al. | β | 2022 | β |
| Abnormal neocortex arealization and Sotos-like syndrome-associated behavior in <i>Setd2</i> mutant mice. | Xu L et al. | β | 2021 | β |
| A class I odorant receptor enhancer shares a functional motif with class II enhancers. | Iwata T et al. | β | 2021 | β |
| A loss-of-function variant in SUV39H2 identified in autism-spectrum disorder causes altered H3K9 trimethylation and dysregulation of protocadherin Ξ²-cluster genes in the developing brain. | Balan S et al. | β | 2021 | β |
| May the Odds Be Ever in Your Favor: Non-deterministic Mechanisms Diversifying Cell Surface Molecule Expression. | Williams DL et al. | β | 2021 | β |
| Mechanism of REST/NRSF regulation of clustered protocadherin Ξ± genes. | Tang Y et al. | β | 2021 | β |
| Mechanism of REST/NRSF Regulation of Clustered Protocadherin Ξ± Genes | Tang Y et al. | β | 2021 | β |
| Wiring the Brain by Clustered Protocadherin Neural Codes. | Wu Q et al. | β | 2021 | β |
| Complex Interactions between Cohesin and CTCF in Regulation of Kaposi's Sarcoma-Associated Herpesvirus Lytic Transcription. | Li D et al. | β | 2020 | β |
| Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection. | Jia Z et al. | β | 2020 | β |
| Three-dimensional genome architectural CCCTC-binding factor makes choice in duplicated enhancers at PcdhΞ± locus. | Wu Y et al. | β | 2020 | β |
| CRISPR/Cas9 interrogation of the mouse Pcdhg gene cluster reveals a crucial isoform-specific role for Pcdhgc4. | Garrett AM et al. | β | 2019 | β |
| Developmental analyses of mouse embryos and adults using a non-overlapping tracing system for all three germ layers. | Serizawa T et al. | β | 2019 | β |
| Enhancer accessibility and CTCF occupancy underlie asymmetric TAD architecture and cell type specific genome topology. | Barrington C et al. | β | 2019 | β |
| Genetic evidence for asymmetric blocking of higher-order chromatin structure by CTCF/cohesin. | Lu Y et al. | β | 2019 | β |
| Snf2h Drives Chromatin Remodeling to Prime Upper Layer Cortical Neuron Development. | Alvarez-Saavedra M et al. | β | 2019 | β |
| Combinatorial Effects of Alpha- and Gamma-Protocadherins on Neuronal Survival and Dendritic Self-Avoidance. | Ing-Esteves S et al. | β | 2018 | β |
| Enhancer hubs and loop collisions identified from single-allele topologies. | Allahyar A et al. | β | 2018 | β |
| Increased H3K9 methylation and impaired expression of Protocadherins are associated with the cognitive dysfunctions of the Kleefstra syndrome. | Iacono G et al. | β | 2018 | β |
| Sox11 gene disruption causes congenital anomalies of the kidney and urinary tract (CAKUT). | Neirijnck Y et al. | β | 2018 | β |
| Writing, Reading, and Translating the Clustered Protocadherin Cell Surface Recognition Code for Neural Circuit Assembly. | Mountoufaris G et al. | β | 2018 | β |
| A long-range cis-regulatory element for class I odorant receptor genes. | Iwata T et al. | β | 2017 | β |
| A protocadherin gene cluster regulatory variant is associated with nicotine withdrawal and the urge to smoke. | Jensen KP et al. | β | 2017 | β |
| Epigenetic dysregulation of protocadherins in human disease. | El Hajj N et al. | β | 2017 | β |
| Regulation of clustered protocadherin genes in individual neurons. | Hirayama T et al. | β | 2017 | β |
| Regulation of Wnt signaling by protocadherins. | Mah KM et al. | β | 2017 | β |
| SMCHD1 regulates a limited set of gene clusters on autosomal chromosomes. | Mason AG et al. | β | 2017 | β |
| The methyltransferase SETDB1 regulates a large neuron-specific topological chromatin domain. | Jiang Y et al. | β | 2017 | β |
| Aberrant expression and functions of protocadherins in human malignant tumors. | Shan M et al. | β | 2016 | β |
| Characterization of a Single Genomic Locus Encoding the Clustered Protocadherin Receptor Diversity in Xenopus tropicalis. | Etlioglu HE et al. | β | 2016 | β |
| CRISPR Double Cutting through the Labyrinthine Architecture of 3D Genomes. | Huang H et al. | β | 2016 | β |
| Distinct and Cooperative Functions for the <i>Protocadherin</i>-Ξ±, -Ξ² and -Ξ³ Clusters in Neuronal Survival and Axon Targeting. | Hasegawa S et al. | β | 2016 | β |
| Establishment of high reciprocal connectivity between clonal cortical neurons is regulated by the Dnmt3b DNA methyltransferase and clustered protocadherins. | Tarusawa E et al. | β | 2016 | β |
| The Ξ³-Protocadherin-C3 isoform inhibits canonical Wnt signalling by binding to and stabilizing Axin1 at the membrane. | Mah KM et al. | β | 2016 | β |
| Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse. | Isbel L et al. | β | 2016 | β |
| CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function. | Guo Y et al. | β | 2015 | β |
| Epigenetic events regulating monoallelic gene expression. | Massah S et al. | β | 2015 | β |
| Protocadherins branch out: Multiple roles in dendrite development. | Keeler AB et al. | β | 2015 | β |
| Structure and Sequence Analyses of Clustered Protocadherins Reveal Antiparallel Interactions that Mediate Homophilic Specificity. | Nicoludis JM et al. | β | 2015 | β |
| The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues. | Cuadrado A et al. | β | 2015 | β |
| Developmental epigenetic modification regulates stochastic expression of clustered protocadherin genes, generating single neuron diversity. | Toyoda S et al. | β | 2014 | β |
| Expansion of stochastic expression repertoire by tandem duplication in mouse Protocadherin-Ξ± cluster. | Kaneko R et al. | β | 2014 | β |
| Protocadherins in neurological diseases. | Hirabayashi T et al. | β | 2014 | β |
| Clustered protocadherins. | Chen WV et al. | β | 2013 | β |
| Clustered protocadherins and neuronal diversity. | Hirayama T et al. | β | 2013 | β |
| Genetic basis of neuronal individuality in the mammalian brain. | Yagi T | β | 2013 | β |
| Protocadherins, not prototypical: a complex tale of their interactions, expression, and functions. | Weiner JA et al. | β | 2013 | β |
| Role of self-avoidance in neuronal wiring. | Kise Y et al. | β | 2013 | β |
| Smchd1 regulates a subset of autosomal genes subject to monoallelic expression in addition to being critical for X inactivation. | Mould AW et al. | β | 2013 | β |
| Constitutively expressed Protocadherin-Ξ± regulates the coalescence and elimination of homotypic olfactory axons through its cytoplasmic region. | Hasegawa S et al. | β | 2012 | β |
| CTCF/cohesin-mediated DNA looping is required for protocadherin Ξ± promoter choice. | Guo Y et al. | β | 2012 | β |
| CTCF is required for neural development and stochastic expression of clustered Pcdh genes in neurons. | Hirayama T et al. | β | 2012 | β |
| Functional significance of isoform diversification in the protocadherin gamma gene cluster. | Chen WV et al. | β | 2012 | β |
| Identification of CTCF as a master regulator of the clustered protocadherin genes. | Golan-Mashiach M et al. | β | 2012 | β |
| Molecular codes for neuronal individuality and cell assembly in the brain. | Yagi T | β | 2012 | β |
| Novel transcriptional targets of the SRY-HMG box transcription factor SOX4 link its expression to the development of small cell lung cancer. | Castillo SD et al. | β | 2012 | β |
| Role of CCCTC binding factor (CTCF) and cohesin in the generation of single-cell diversity of protocadherin-Ξ± gene expression. | Monahan K et al. | β | 2012 | β |
| Single-neuron diversity generated by Protocadherin-Ξ² cluster in mouse central and peripheral nervous systems. | Hirano K et al. | β | 2012 | β |
| Regulatory elements required for the activation and repression of the protocadherin-alpha gene cluster. | Kehayova P et al. | β | 2011 | β |