Ocat, a paternally expressed gene closely linked and transcribed in the opposite direction to Peg3.

Two reciprocally imprinted Kruppel-type zinc finger genes, Peg3 and Zim1, have been found in close proximity on mouse proximal chromosome 7. Here, we describe the identification of another novel imprinted transcript, Ocat (ossification center-associated transcript). Ocat encodes a 5.5-kb spliced transcript and is transcribed in the opposite orientation to Peg3. One of its exons (putative exon 1) lies approximately 200 bp upstream of Peg3. Ocat is predominantly expressed in embryos from days 11 to 17, particularly in ossification centers of the embryonic skeleton at day 15. Like Peg3, Ocat is expressed exclusively from the paternal allele. Despite their proximity, Peg3 and Ocat showed dissimilar expression profiles, suggesting that they are regulated by independent genetic elements.

Szeto IY ，Li LL ，Surani MA 《GENOMICS》

Peg3 imprinted gene on proximal chromosome 7 encodes for a zinc finger protein.

Kuroiwa Y ，Kaneko-Ishino T ，Kagitani F ，Kohda T ，Li LL ，Tada M ，Suzuki R ，Yokoyama M ，Shiroishi T ，Wakana S ，Barton SC ，Ishino F ，Surani MA ... -  《NATURE GENETICS》

Organization and parent-of-origin-specific methylation of imprinted Peg3 gene on mouse proximal chromosome 7.

Peg3 is the first imprinted gene to be identified on mouse proximal chromosome 7; the human PEG3 homologue is on chromosome 19q13.4. Peg3 encodes a C(2)H(2)-type zinc finger protein that is expressed only from the paternal allele in embryos and adult brain. The gene has been shown to regulate maternal behavior and offspring growth and has been implicated in the TNF-NFkappaB signal pathway. Here we show that Peg3 consists of nine exons spanning 26 kb. The 5' region of the gene contains a region rich in repeated sequences and a CpG island. Analysis of expressed sequence tags revealed a transcript present upstream of the island and on the strand opposite to Peg3. These structural features and DNA sequences are conserved in mouse and human. The 5' region of Peg3 is preferentially methylated on the inactive maternal allele, as shown by comparing embryos with paternal (PatDp. prox7) and maternal (MatDp.prox7) duplication of proximal chromosome 7. Recently, a new maternally expressed Zim1 gene located downstream of Peg3 was identified, which suggested that another imprinted cluster is present on proximal chromosome 7.

Li LL ，Szeto IY ，Cattanach BM ，Ishino F ，Surani MA ... -  《GENOMICS》

Exon sharing of a novel human zinc-finger gene, ZIM2, and paternally expressed gene 3 (PEG3).

We have identified a novel human gene, ZIM2 (zinc-finger gene 2 from imprinted domain), located 25 kb downstream of PEG3 (paternally expressed gene 3). ZIM2 produces two different-size transcripts, 2.5 and 9.0 kb in length, with highest levels of expression in adult testis and modest levels in fetal kidney and brain. The 2.5-kb transcript of ZIM2 consists of 11 exons and encodes a Kruppel-type (C2H2) zinc-finger protein with a conserved Kruppel-associated box (KRAB) domain. Rapid amplification of cDNA ends and cDNA sequencing studies showed that ZIM2 and PEG3 transcripts share identical 5'-ends, composed of 7 small exons. Alternative splicing events connect these 7 exons either with the remaining 2 exons of PEG3 or with the remaining 4 exons of ZIM2. Interestingly, the third among the 7 shared exons exhibits sequence similarity to leucine-rich domains that are found at the N-terminal region of a subset of KRAB-containing zinc-finger genes. Sequencing of the 5'-termini of both transcripts indicates that ZIM2 and PEG3 share identical transcription start sites and may also share upstream regulatory elements, although the two genes show distinct patterns of tissue-specific expression.

Kim J ，Bergmann A ，Stubbs L 《GENOMICS》

Imprinting of PEG3, the human homologue of a mouse gene involved in nurturing behavior.

The paternally expressed Peg3 gene in mice encodes an unusual Krüppel-type zinc finger protein implicated in critical cellular and behavioral functions including growth, apoptosis, and maternal nurturing behavior. Methylation and expression analyses were used to determine whether PEG3 on chromosome 19q13.4 is imprinted in humans. The PEG3 promoter is encompassed within a large CpG-rich region that is differentially methylated in fetal tissues. Furthermore, expression studies demonstrate that PEG3 is ubiquitously imprinted throughout development and postnatally. Multiple isoforms of the PEG3 gene, including a novel transcript, are paternally expressed. These results are the first to show that human chromosome 19q13.4 contains an imprinted region. The imprinted status of PEG3 throughout life coupled with its neural expression and putative roles in regulating cell growth suggests that PEG3 may be a susceptibility locus for cancer as well as neurobehavioral deficits.

Murphy SK ，Wylie AA ，Jirtle RL 《GENOMICS》