Clustered organization of homologous KRAB zinc-finger genes with enhanced expression in human T lymphoid cells.

Abstract

KRAB zinc‐finger proteins (KRAB‐ZFPs) constitute a large subfamily of ZFPs of the Krüppel C2H2 type. KRAB (Krüppel‐associated box) is an evolutionarily conserved protein domain found N‐terminally with respect to the finger repeats. We report here the characterization of a particular subgroup of highly related human KRAB‐ZFPs. ZNF91 is one representative of this subgroup and contains 35 contiguous finger repeats at its C‐terminus. Three mRNA isoforms with sequence identity to ZNF91 were isolated by the polymerase chain reaction. These encode proteins with a KRAB domain present, partially deleted or absent. Five genomic fragments were characterized, each encoding part of a gene: the ZNF91 gene or one of four distinct, related KRAB‐ZFP genes. All exhibit a common exon/intron organization with the variant zinc finger repeats organized in a single exon and the KRAB domain encoded by two separate exons. This positioning of introns supports the hypothesis that the mRNA isoforms encoding polypeptides with variability in the KRAB domain could arise by alternative splicing. By in situ chromosomal mapping studies and by analysis of fragments from a human genomic yeast artificial chromosome library containing KRAB‐ZFP genes, we show that these genes occur in clusters; in particular, a gene complex containing over 40 genes has been identified in chromosomal region 19p12‐p13.1. These ZNF91‐related genes probably arose late during evolution since no homologous genes are detected in the mouse and rat genomes. Although the transcription of members of this KRAB‐ZFP gene subgroup is detectable in all human tissues, their expression is significantly higher in human T lymphoid cells.

Sequence‐Specific Recognition of a Repetitive DNA Element by a C2H2 Zinc‐Finger Protein in Xenopus

“…The various non-conserved clusters of structurally related zinc finger proteins described in amphibians (Nietfeld et al, 1993), rodents (Bianchi et al, 1992) and primates (Bellefroid et al, 1993;Tunnacliffe et al, 1993) appear to be the product of recent gene duplication/amplification events. The nonconserved nature of these ZFPs could correlate with an equally late evolution of their nucleic acid target structures.…”

The KRAB Domain of Zinc Finger Gene ZNF268: a Potential Transcriptional Repressor

“…The KRAB domain can be divided into an A and a B box on the basis of common intron-exon boundaries (10,11).…”

Silencing of RNA Polymerases II and III-Dependent Transcription by the KRAB Protein Domain of KOX1, a Krüppel-Type Zinc Finger Factor

“…It does not occur in yeast and probably not in Drosophila, suggesting its late appearance in evolution. The distinct spatial and temporal expression pattern of several KRAB domain-containing zinc finger factors may indicate an important role in cell differentiation and development, however, their actual function remains to be elucidated (Bellefroid et a/., 1991(Bellefroid et a/., , 1993Witzgall et a/., 1993). The KRAB domain of the human zinc finger proteins KOX1 and Kid-1 have been most extensively studied so far.…”