PMID- 10097123
OWN - NLM
STAT- MEDLINE
DCOM- 19990512
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 7
DP  - 1999 Mar 30
TI  - A cluster of oppositely imprinted transcripts at the Gnas locus in the distal
      imprinting region of mouse chromosome 2.
PG  - 3830-5
AB  - Imprinted genes tend to occur in clusters. We have identified a cluster in distal
      mouse chromosome (Chr) 2, known from early genetic studies to contain both
      maternally and paternally imprinted, but unspecified, genes. Subsequently, one
      was identified as Gnas, which encodes a G protein alpha subunit, and there is
      clinical and biochemical evidence that the human homologue GNAS1, mutated in
      patients with Albright hereditary osteodystrophy, is also imprinted. We have used
      representational difference analysis, based on parent-of-origin methylation
      differences, to isolate candidate imprinted genes in distal Chr 2 and found two
      oppositely imprinted genes, Gnasxl and Nesp. Gnasxl determines a variant G
      protein alpha subunit associated with the trans-Golgi network and Nesp encodes a 
      secreted protein of neuroendocrine tissues. Gnasxl is maternally methylated in
      genomic DNA and encodes a paternal-specific transcript, whereas Nesp is
      paternally methylated with maternal-specific expression. Their reciprocal
      imprinting may offer insight into the distal Chr 2 imprinting phenotypes.
      Remarkably, Gnasxl, Nesp, and Gnas are all part of the same transcription unit;
      transcripts for Gnasxl and Nesp are alternatively spliced onto exon 2 of Gnas.
      This demonstrates an imprinting mechanism in which two oppositely imprinted genes
      share the same downstream exons.
FAU - Peters, J
AU  - Peters J
AD  - Mammalian Genetics Unit, Medical Research Council, Harwell, Didcot, Oxfordshire, 
      OX11 0RD, United Kingdom. j.peters@har.mrc.ac.uk
FAU - Wroe, S F
AU  - Wroe SF
FAU - Wells, C A
AU  - Wells CA
FAU - Miller, H J
AU  - Miller HJ
FAU - Bodle, D
AU  - Bodle D
FAU - Beechey, C V
AU  - Beechey CV
FAU - Williamson, C M
AU  - Williamson CM
FAU - Kelsey, G
AU  - Kelsey G
LA  - eng
SI  - GENBANK/AF125257
SI  - GENBANK/AF125259
SI  - GENBANK/AF125315
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
SB  - IM
MH  - Alternative Splicing
MH  - Animals
MH  - Animals, Newborn
MH  - Base Sequence
MH  - *Chromosome Mapping
MH  - DNA Methylation
MH  - Embryo, Mammalian
MH  - Exons
MH  - Female
MH  - Fibrous Dysplasia, Polyostotic/genetics
MH  - GTP-Binding Protein alpha Subunits, Gs/*genetics
MH  - Gene Expression Regulation, Developmental
MH  - Genomic Imprinting
MH  - Humans
MH  - Male
MH  - Mice/*genetics
MH  - Mice, Mutant Strains
MH  - Molecular Sequence Data
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Alignment
MH  - Sequence Homology, Nucleic Acid
MH  - Transcription, Genetic
PMC - PMC22380
EDAT- 1999/03/31 00:00
MHDA- 1999/03/31 00:01
CRDT- 1999/03/31 00:00
PHST- 1999/03/31 00:00 [pubmed]
PHST- 1999/03/31 00:01 [medline]
PHST- 1999/03/31 00:00 [entrez]
AID - 10.1073/pnas.96.7.3830 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3830-5. doi: 10.1073/pnas.96.7.3830.