Human ZNF295 protein harbors a BTB/POZ domain and multiple kruppel (C2H2) type zinc finger domains, and thus belongs to a family of POK (POZ and kruppel) transcription factor. We have identified many transcript variants generated by the alternative splicing in 5' non-coding exons, an intra-exonic splicing in a coding region, and the use of three polyadenylation signals in the 3' UTR. The intra-exonic splicing removes 603-bp coding sequence, and thus ZNF295 gene produces two protein isoforms: ZNF295L with 1066 amino acid residues and ZNF295S with 865 amino acid residues, containing 9 and 5 zinc finger domains, respectively. ZNF295 is ubiquitously expressed in human fetal and adult tissues. Analysis of transcription activity of ZNNF-295 using various promoter-reporters demonstrated that ZNF295 acts as a transcription repressor, and contains two separate regions for repression activity: the BTB/POZ domain and the central region between BTB/POZ and ZF domains. Both ZNF295L and ZNF295S could interact not only with themselves and each other, but also with another POK protein ZFP161 known to function as a transcription repressor and an activator. We postulated that ZNF295 may be involved in the bi-directional control of gene expression in concert, with ZFP161. (C) 2004 Elsevier Inc. All rights reserved.