| First Author | Ribich S | Year | 2006 |
| Journal | Proc Natl Acad Sci U S A | Volume | 103 |
| Issue | 52 | Pages | 19719-24 |
| PubMed ID | 17172445 | Mgi Jnum | J:118324 |
| Mgi Id | MGI:3699437 | Doi | 10.1073/pnas.0609445104 |
| Citation | Ribich S, et al. (2006) Identification of long-range regulatory elements in the protocadherin-alpha gene cluster. Proc Natl Acad Sci U S A 103(52):19719-24 |
| abstractText | The clustered protocadherins (Pcdh) are encoded by three closely linked gene clusters (Pcdh-alpha, -beta, and -gamma) that span nearly 1 million base pairs of DNA. The Pcdh-alpha gene cluster encodes a family of 14 distinct cadherin-like cell surface proteins that are expressed in neurons and are present at synaptic junctions. Individual Pcdh-alpha mRNAs are assembled from one of 14 'variable' (V) exons and three 'constant' exons in a process that involves both differential promoter activation and alternative pre-mRNA splicing. In individual neurons, only one (and rarely two) of the Pcdh alpha1-12 promoters is independently and randomly activated on each chromosome. Thus, in most cells, this unusual form of monoallelic expression leads to the expression of two different Pcdh-alpha 1-12 V exons, one from each chromosome. The two remaining V exons in the cluster (Pcdh-alphaC1 and alphaC2) are expressed biallelically in every neuron. The mechanisms that underlie promoter choice and monoallelic expression in the Pcdh-alpha gene cluster are not understood. Here we report the identification of two long-range cis-regulatory elements in the Pcdh-alpha gene cluster, HS5-1 and HS7. We show that HS5-1 is required for maximal levels of expression from the Pcdh alpha1-12 and alphaC1 promoters, but not the Pcdh-alphaC2 promoter. The nearly cluster-wide requirement of the HS5-1 element is consistent with the possibility that the monoallelic expression of Pcdh-alpha V exons is a consequence of competition between individual V exon promoters for the two regulatory elements. |
