title: Isolation and characterization of a novel gene from the DiGeorge chromosomal region that encodes for a mediator subunit.
abstract: Hemizygous deletions on chromosome 22q11.2 result in developmental disorders referred to as DiGeorge syndrome (DGS)/velocardiofacial syndrome (VCFS). We report the isolation of a novel gene, PCQAP (PC2 glutamine/Q-rich-associated protein), that maps to the DiGeorge typically deleted region and encodes a protein identified as a subunit of the large multiprotein complex PC2. PC2 belongs to the family of the human Mediator complexes, which exhibit coactivator function in RNA polymerase II transcription. Furthermore, we cloned the homologous mouse Pcqap cDNA. There is 83% amino acid identity between the human and the mouse predicted protein sequences, with 96% similarity at the amino- and carboxy-terminal ends. To assess the potential involvement of PCQAP in DGS/VCFS, its developmental expression pattern was analyzed. In situ hybridization of mouse embryos at different developmental stages revealed that Pcqap is ubiquitously expressed. However, higher expression was detected in the frontonasal region, pharyngeal arches, and limb buds. Moreover, analysis of subjects carrying a typical 22q11 deletion revealed that the human PCQAP gene was deleted in all patients. Many of the structures affected in DGS/VCFS evolve from Pcqap-expressing cells. Together with the observed haploinsufficiency of PCQAP in DGS/VCFS patients, this finding is consistent with a possible role for this novel Mediator subunit in the development of some of the structures affected in DGS/VCFS.
authors: Department of Protein Biochemistry, Institute of Molecular Immunology-GSF, Munich, 81377, Germany.
authors: L
authors: L
authors: Berti
authors: G
authors: G
authors: Mittler
authors: G K
authors: GK
authors: Przemeck
authors: G
authors: G
authors: Stelzer
authors: B
authors: B
authors: Günzler
authors: F
authors: F
authors: Amati
authors: E
authors: E
authors: Conti
authors: B
authors: B
authors: Dallapiccola
authors: M
authors: M
authors: Hrabé de Angelis
authors: G
authors: G
authors: Novelli
authors: M
authors: M
authors: Meisterernst
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D004062:DiGeorge Syndrome / Q000235:genetics*; D004622:Embryo, Mammalian / Q000378:metabolism; D005091:Exons; D005260:Female; D015870:Gene Expression; D005796:Genes / Q000235:genetics; D005973:Glutamine / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D019169:Jurkat Cells; D008297:Male; D056892:Mediator Complex; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; C416944:MED15 protein, human; C485939:Med 15 protein, mouse; D056892:Mediator Complex; D021122:Protein Subunits; D012333:RNA, Messenger; D014157:Transcription Factors; D005973:Glutamine