A very small subset of mammalian genes, about 100 to 200 genes in each genome, are subject to an unusual dosage control called ‘Genomic Imprinting.’ In these imprinted genes, only one of two parental alleles is expressed and functional. Due to this functional hemizygosity, many imprinted genes are associated with human genetic disorders. In the past several years, our laboratory has characterized one of imprinted domains located in human chromosome 19q13.4/ proximal mouse chromosome 7. This domain harbors 6 imprinted genes, including paternally expressed Peg3, Usp29, Zfp264, and maternally expressed Zim1, Zim2, Zim3. Our lab is interested in investigating imprinting regulatory mechanism and the functions of each imprinted gene.
The first direction of our lab project is to understand molecular mechanisms governing the imprinting (mono-allelic expression) of these six genes. We have identified a genomic region that may be responsible for the imprinting of this domain. This region located within the first intron of Peg3 (Paternally expressed gene 3) contains a very unusual tandem array of multiple YY1 binding sites. YY1 is a well-known transcription factor controlling many mammalian genes. We are currently studying the potential mechanism by which YY1 controls the imprinting of the six genes. With bioinformatic tools, we have also analyzed all the available genome sequences to identify unknown regulatory regions with similar tandem arrays of YY1 binding sites. We are analyzing several newly identified YY1 binding sites that are also located within other imprinted domains.
The second direction is to understand the function of each imprinted gene. Most imprinted genes in the Peg3-domain are predicted to be DNA-binding transcription factors. In particular, Peg3 is known to control maternal caring behaviors and fetal growth rates. Other studies also suggest that human PEG3 is most likely a tumor suppressor gene. To characterize the functions of this transcription factor, we are characterizing binding motifs as well as potential ‘downstream’ genes of this imprinted gene using Chromatin ImmunoPrecipitation (ChIP)-based approaches and bioinformatic tools.
Publications (since 2015)
B.P.U. Perera and J. Kim (2016). Alternative promoters of Peg3 with maternal specificity. Sci. Rep. 6: 24438.
Lee, A. Ye, and J. Kim (2015). DNA-binding motif of the imprinted transcription factor PEG3. PLoS ONE 10(12): e0145531.
C.L. Bretz, I. Langohr, S. Lee, and J. Kim (2015). Epigenetic instability at imprinting control regions in a KrasG12D T-cell neoplasm. Epigenetics 10(12): 1111-1120.
J. Kim, C.L. Bretz, S. Lee (2015). Epigenetic instability of imprinted genes in human cancers. Nucleic Acids Res 43(22): 10689-10699.