TY - JOUR
T1 - The human HYMAI/PLAGL1 differentially methylated region acts as an imprint control region in mice
AU - Arima, Takahiro
AU - Yamasaki, Katsuhisa
AU - John, Rosalind M.
AU - Kato, Kiyoko
AU - Sakumi, Kunihiko
AU - Nakabeppu, Yusaku
AU - Wake, Norio
AU - Kono, Tomohiro
N1 - Funding Information:
We thank Y. Yoshikawa and T. Nakashima for technical assistance and the company Macrogen, Inc. (Seoul, Korea), for making transgenic mice by the method of microinjection, and all our lab members for their support and valuable suggestions. This work was supported by a grant from the Ministry of Health and Welfare of Japan.
PY - 2006/11
Y1 - 2006/11
N2 - Imprinting centers (IC) can be defined as cis-elements that are recognized in the germ line and are epigenetically modified to bring about the full imprinting program in a somatic cell. Two paternally expressed human genes, HYMAI and PLAGL1 (LOT1/ZAC), are located within human chromosome 6q24. Within this region lies a 1-kb CpG island that is differentially methylated in somatic cells, unmethylated in sperm, and methylated in mature oocytes in mice, characteristic features of an IC. Loss of methylation of the homologous region in humans is observed in patients with transient neonatal diabetes mellitus and hypermethylation is associated with a variety of cancers, suggesting that this region regulates the expression of one or more key genes in this region involved in these diseases. We now report that a transgene carrying the human HYMAI/PLAGL1 DMR was methylated in the correct parent-origin-specific manner in mice and this was sufficient to confer imprinted expression from the transgene. Therefore, we propose that this DMR functions as the IC for the HYMAI/PLAGL1 domain.
AB - Imprinting centers (IC) can be defined as cis-elements that are recognized in the germ line and are epigenetically modified to bring about the full imprinting program in a somatic cell. Two paternally expressed human genes, HYMAI and PLAGL1 (LOT1/ZAC), are located within human chromosome 6q24. Within this region lies a 1-kb CpG island that is differentially methylated in somatic cells, unmethylated in sperm, and methylated in mature oocytes in mice, characteristic features of an IC. Loss of methylation of the homologous region in humans is observed in patients with transient neonatal diabetes mellitus and hypermethylation is associated with a variety of cancers, suggesting that this region regulates the expression of one or more key genes in this region involved in these diseases. We now report that a transgene carrying the human HYMAI/PLAGL1 DMR was methylated in the correct parent-origin-specific manner in mice and this was sufficient to confer imprinted expression from the transgene. Therefore, we propose that this DMR functions as the IC for the HYMAI/PLAGL1 domain.
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U2 - 10.1016/j.ygeno.2006.07.005
DO - 10.1016/j.ygeno.2006.07.005
M3 - Article
C2 - 16928428
AN - SCOPUS:33749599736
SN - 0888-7543
VL - 88
SP - 650
EP - 658
JO - Genomics
JF - Genomics
IS - 5
ER -
