Title:
METHODS FOR ASSAYING GENE IMPRINTING AND METHYLATED CpG ISLANDS
Document Type and Number:
WIPO Patent Application WO2001090313
Kind Code:
A3
Abstract:
Genomic imprinting is a parent of origin-dependent gene silencing that involves marking of alleles in the germline and differential expression in somatic cells of the offspring. Imprinted genes and abnormal imprinting have been implicated in development, human disease, and embryonic stem cell transplantation. We have established a model system for genomic imprinting using pluripotent 8.5 d.p.c. mouse embryonic germ (EG) cell lines derived from an interspecific cross. We find that allele-specific imprinted gene expression has been lost in these cells. However, partial restoration of allele-specific silencing can occur for some imprinted genes after in vitro differentiation of EG cells into somatic cell lineages, indicating the presence of a gametic memory that is separable from allele-specific gene silencing. We have also generated a library containing most methylated CpG islands. A subset of these clones was analyzed and revealed a subdivision of methylated CpG islands into 4 distinct subtypes: CpG islands belonging to high copy number repeat families; unique CpG islands methylated in all tissues; unique methylated CpG islands that are unmethylated in the paternal germline; and unique CpG islands methylated in tumors. This approach identifies a methylome of methylated CpG islands throughout the genome.
Inventors:
FEINBERG ANDREW (US)
STRICHMAN-ALMASHANU LIORA (US)
JIANG SHAN (US)
STRICHMAN-ALMASHANU LIORA (US)
JIANG SHAN (US)
Application Number:
PCT/US2001/016253
Publication Date:
May 16, 2002
Filing Date:
May 22, 2001
Export Citation:
Assignee:
UNIV JOHNS HOPKINS (US)
FEINBERG ANDREW (US)
STRICHMAN ALMASHANU LIORA (US)
JIANG SHAN (US)
FEINBERG ANDREW (US)
STRICHMAN ALMASHANU LIORA (US)
JIANG SHAN (US)
International Classes:
A61P35/00; C12N5/074; C12N5/10; C12N15/09; C12Q1/02; C12Q1/68; A01K67/027; (IPC1-7): C12N5/06; C12Q1/68; C12N15/11; A01K67/027; G01N33/50; A61P35/00
Domestic Patent References:
| WO2000026401A1 | 2000-05-11 | |||
| WO2000004187A2 | 2000-01-27 |
Other References:
LABOSKY PATRICIA A ET AL: "Mouse embryonic germ (EG) cell lines: Transmission through the germline and differences in the methylation imprint of insulin-like growth factor 2 receptor (Igf2r) gene compared with embryonic stem (ES) cell lines.", DEVELOPMENT (CAMBRIDGE), vol. 120, no. 11, 1994, pages 3197 - 3204, XP008000839, ISSN: 0950-1991
MATSUI Y ET AL: "DERIVATION OF PLURIPOTENTIAL EMBRYONIC STEM CELLS FROM MURINE PRIMORDIAL GERM CELLS IN CULTURE", CELL, CELL PRESS, CAMBRIDGE, NA, US, vol. 70, 4 September 1992 (1992-09-04), pages 841 - 847, XP002912252, ISSN: 0092-8674
MITSUYA KOHZOH ET AL: "Epigenetic reprogramming of the human H19 gene in mouse embryonic cells does not erase the primary parental imprint.", GENES TO CELLS, vol. 3, no. 4, April 1998 (1998-04-01), pages 245 - 255, XP001061253, ISSN: 1356-9597
OGAWA O ET AL: "RELAXATION OF INSULIN-LIKE GROWTH FACTOR II gene imprinting implicated in Wilms' tumor", NATURE, MACMILLAN JOURNALS LTD. LONDON, GB, vol. 362, 22 April 1993 (1993-04-22), pages 749 - 751, XP002129284, ISSN: 0028-0836
OVERALL MAREE ET AL: "Genomic imprinting in the rat: Linkage of Igf2 and H19 genes and opposite parental allele-specific expression during embryogenesis.", GENOMICS, vol. 45, no. 2, 1997, pages 416 - 420, XP002191365, ISSN: 0888-7543
SUTCLIFFE J S ET AL: "DELETIONS OF A DIFFERENTIALLY METHYLATED CPG ISLAND AT THE SNRPN GENE DEFINE A PUTATIVE IMPRINTING CONTROL REGION", NATURE GENETICS, NEW YORK, NY, US, vol. 8, September 1994 (1994-09-01), pages 52 - 58, XP002912861, ISSN: 1061-4036
HAYWARD B E ET AL: "BIDIRECTIONAL IMPRINTING OF A SINGLE GENE: GNAS1 ENCODES MATERNALLY, PATERNALLY, AND BIALLELICALLY DERIVED PROTEINS", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE. WASHINGTON, US, vol. 95, December 1998 (1998-12-01), pages 15475 - 15480, XP000946062, ISSN: 0027-8424
LEE C K ET AL: "Isolation and genetic transformation of primordial germ cell (PGC)-derived cells from cattle, goats, rabbits and rats.", ASIAN-AUSTRALASIAN JOURNAL OF ANIMAL SCIENCES, vol. 13, no. 5, May 2000 (2000-05-01), pages 587 - 594, XP001061288, ISSN: 1011-2367
DATABASE BIOSIS BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; GREGOROVA S ET AL, XP002191368
MATSUI Y ET AL: "DERIVATION OF PLURIPOTENTIAL EMBRYONIC STEM CELLS FROM MURINE PRIMORDIAL GERM CELLS IN CULTURE", CELL, CELL PRESS, CAMBRIDGE, NA, US, vol. 70, 4 September 1992 (1992-09-04), pages 841 - 847, XP002912252, ISSN: 0092-8674
MITSUYA KOHZOH ET AL: "Epigenetic reprogramming of the human H19 gene in mouse embryonic cells does not erase the primary parental imprint.", GENES TO CELLS, vol. 3, no. 4, April 1998 (1998-04-01), pages 245 - 255, XP001061253, ISSN: 1356-9597
OGAWA O ET AL: "RELAXATION OF INSULIN-LIKE GROWTH FACTOR II gene imprinting implicated in Wilms' tumor", NATURE, MACMILLAN JOURNALS LTD. LONDON, GB, vol. 362, 22 April 1993 (1993-04-22), pages 749 - 751, XP002129284, ISSN: 0028-0836
OVERALL MAREE ET AL: "Genomic imprinting in the rat: Linkage of Igf2 and H19 genes and opposite parental allele-specific expression during embryogenesis.", GENOMICS, vol. 45, no. 2, 1997, pages 416 - 420, XP002191365, ISSN: 0888-7543
SUTCLIFFE J S ET AL: "DELETIONS OF A DIFFERENTIALLY METHYLATED CPG ISLAND AT THE SNRPN GENE DEFINE A PUTATIVE IMPRINTING CONTROL REGION", NATURE GENETICS, NEW YORK, NY, US, vol. 8, September 1994 (1994-09-01), pages 52 - 58, XP002912861, ISSN: 1061-4036
HAYWARD B E ET AL: "BIDIRECTIONAL IMPRINTING OF A SINGLE GENE: GNAS1 ENCODES MATERNALLY, PATERNALLY, AND BIALLELICALLY DERIVED PROTEINS", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE. WASHINGTON, US, vol. 95, December 1998 (1998-12-01), pages 15475 - 15480, XP000946062, ISSN: 0027-8424
LEE C K ET AL: "Isolation and genetic transformation of primordial germ cell (PGC)-derived cells from cattle, goats, rabbits and rats.", ASIAN-AUSTRALASIAN JOURNAL OF ANIMAL SCIENCES, vol. 13, no. 5, May 2000 (2000-05-01), pages 587 - 594, XP001061288, ISSN: 1011-2367
DATABASE BIOSIS BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; GREGOROVA S ET AL, XP002191368
Download PDF: