Coding region intron/exon organization, alternative splicing, and X-chromosome inactivation of the KRAB/FPB-domain-containing human zinc finger gene ZNF41

ZNF41 belongs to a cluster of human zinc finger genes residing within a gen e-rich region at Xp11.23. ZNF41 encodes a KRAB/FPB (Kruppel-associated/fing er preceding box) domain, a potent transcription repression motif present i n hundreds of vertebrate zinc finger protein genes, composed of two protein modules, A and B. Three introns, placed at identical positions in paralogo us genes, interrupt four exons encoding the ZNF41 N-terminal amino acids, t he KRAB/FPB-A and KRAB/FPB-B modules, and the remaining coding region adjoi ned to the C-terminal zinc finger domain. Since the KRAB/FPB-A and KRAB/FPB -B modules are encoded by dedicated exons in ZNF41 and paralogous genes, ex on skipping may lead to differential usage of these modules in alternative gene products. RT-PCR analysis of ZNF41 mRNAs showed that, while skipping o f the KRAB/FPB-A and/or KRAB/FPB-B exons was not detected, the use of alter native donor/acceptor sites upstream of the KRAB/FPB-A exon generates multi ple ZNF41 transcripts potentially encoding polypeptides differing in the N- terminal region and expressed in different tissues. The expression pattern in cell hybrids containing either active or inactive X chromosomes indicate s that ZNF41, which resides within a region of the X chromosome that includ es genes that are both subject to and escape X-inactivation, is susceptible to X-chromosome inactivation.