The human HYMAI/PLAGL1 differentially methylated region acts as an imprint control region in mice

Takahiro Arima; Katsuhisa Yamasaki; Rosalind M. John; Kiyoko Kato; Kunihiko Sakumi; Yusaku Nakabeppu; Norio Wake; Tomohiro Kono

doi:10.1016/j.ygeno.2006.07.005

The human HYMAI/PLAGL1 differentially methylated region acts as an imprint control region in mice

Takahiro Arima, Katsuhisa Yamasaki, Rosalind M. John, Kiyoko Kato, Kunihiko Sakumi, Yusaku Nakabeppu, Norio Wake, Tomohiro Kono

Medicine (department affiliation only)

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	650-658
Number of pages	9
Journal	Genomics
Volume	88
Issue number	5
DOIs	https://doi.org/10.1016/j.ygeno.2006.07.005
Publication status	Published - 2006 Nov

Keywords

DNA methylation
Genomic imprinting
HYMAI/PLAGL1
Imprint control region

ASJC Scopus subject areas

Genetics

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@article{134acdac945944b680c6eeb94ef45afa,

title = "The human HYMAI/PLAGL1 differentially methylated region acts as an imprint control region in mice",

abstract = "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.",

keywords = "DNA methylation, Genomic imprinting, HYMAI/PLAGL1, Imprint control region",

author = "Takahiro Arima and Katsuhisa Yamasaki and John, {Rosalind M.} and Kiyoko Kato and Kunihiko Sakumi and Yusaku Nakabeppu and Norio Wake and Tomohiro Kono",

note = "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. ",

year = "2006",

month = nov,

doi = "10.1016/j.ygeno.2006.07.005",

language = "English",

volume = "88",

pages = "650--658",

journal = "Genomics",

issn = "0888-7543",

publisher = "Academic Press Inc.",

number = "5",

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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.

KW - DNA methylation

KW - Genomic imprinting

KW - HYMAI/PLAGL1

KW - Imprint control region

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