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.
1. J. Kim and J.D. Kim (2008). In vivo YY1-knockdown effects on genomic imprinting. Hum. Mol. Genet. 17, 391-401.
2. J. Kim (2008). Multiple YY1 and CTCF binding sites in Imprinting Control Regions. Epigenetics. 3, 115-118.
3. J.D. Kim, S. Yu, J.H. Choo, and J. Kim (2008). Two evolutionary conserved sequence elements for Peg3/Usp29 transcription. BMC Mol Biol. 9, 108.
4. J.D. Kim and J. Kim (2009). YY1's longer DNA binding motifs. Genomics. 93, 152-158.
5. K. Kang, J.H. Chung, and J. Kim (2009). Evolutionary Conserved Motif Finder (ECMFinder) for genome-wide identification of clustered YY1 and CTCF binding sites.
Nucleic Acids Res. 37, 2003-2013.
6. H. Kim, K. Kang, and J. Kim (2009). AEBP2 as a potential targeting protein for Polycomb Repression Complex PRC2. Nucleic Acids Res. (in press).
7. J.M. Huang and J. Kim (2009). DNA methylation analysis of mammalian Peg3 imprinted domain. Gene. (In press).