Berti L, Mittler G, Przemeck G K, Stelzer G, Günzler B, Amati F, Conti E, Dallapiccola B, Hrabé de Angelis M, Novelli G, Meisterernst M
Department of Protein Biochemistry, Institute of Molecular Immunology-GSF, Munich, 81377, Germany.
Genomics. 2001 Jun 15;74(3):320-32. doi: 10.1006/geno.2001.6566.
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.
22号染色体q11.2区域的半合子缺失会导致被称为DiGeorge综合征（DGS）/心脏颜面综合征（VCFS）的发育障碍。我们报告了一个新基因PCQAP（PC2谷氨酰胺/富含Q蛋白相关蛋白）的分离，该基因定位于DiGeorge综合征典型的缺失区域，并编码一种被鉴定为大型多蛋白复合物PC2亚基的蛋白质。PC2属于人类中介复合物家族，在RNA聚合酶II转录中发挥共激活因子功能。此外，我们克隆了同源的小鼠Pcqap cDNA。人类和小鼠预测的蛋白质序列之间有83%的氨基酸同一性，在氨基和羧基末端有96%的相似性。为了评估PCQAP在DGS/VCFS中的潜在作用，分析了其发育表达模式。对不同发育阶段的小鼠胚胎进行原位杂交显示，Pcqap在全身广泛表达。然而，在前鼻区域、咽弓和肢芽中检测到较高的表达。此外，对携带典型22q11缺失的受试者的分析显示，所有患者的人类PCQAP基因均被删除。许多在DGS/VCFS中受影响的结构都由表达Pcqap的细胞发育而来。结合在DGS/VCFS患者中观察到的PCQAP单倍剂量不足，这一发现与这个新的中介亚基在DGS/VCFS中一些受影响结构的发育中可能发挥的作用一致。
