Genome-wide histone state profiling of fibroblasts from the opossum, Monodelphis domestica, identifies the first marsupial-specific imprinted gene.
BACKGROUND
Imprinted genes have been extensively documented in eutherian mammals and found to exhibit significant interspecific variation in the suites of genes that are imprinted and in their regulation between tissues and developmental stages. Much less is known about imprinted loci in metatherian (marsupial) mammals, wherein studies have been limited to a small number of genes previously known to be imprinted in eutherians. We describe the first ab initio search for imprinted marsupial genes, in fibroblasts from the opossum, Monodelphis domestica, based on a genome-wide ChIP-seq strategy to identify promoters that are simultaneously marked by mutually exclusive, transcriptionally opposing histone modifications.


RESULTS
We identified a novel imprinted gene (Meis1) and two additional monoallelically expressed genes, one of which (Cstb) showed allele-specific, but non-imprinted expression. Imprinted vs. allele-specific expression could not be resolved for the third monoallelically expressed gene (Rpl17). Transcriptionally opposing histone modifications H3K4me3, H3K9Ac, and H3K9me3 were found at the promoters of all three genes, but differential DNA methylation was not detected at CpG islands at any of these promoters.


CONCLUSIONS
In generating the first genome-wide histone modification profiles for a marsupial, we identified the first gene that is imprinted in a marsupial but not in eutherian mammals. This outcome demonstrates the practicality of an ab initio discovery strategy and implicates histone modification, but not differential DNA methylation, as a conserved mechanism for marking imprinted genes in all therian mammals. Our findings suggest that marsupials use multiple epigenetic mechanisms for imprinting and support the concept that lineage-specific selective forces can produce sets of imprinted genes that differ between metatherian and eutherian lines.
Kory C
KC
Douglas
Xu
X
Wang
Madhuri
M
Jasti
Abigail
A
Wolff
John L
JL
VandeBerg
Andrew G
AG
Clark
Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA. psamollow@cvm.tamu.edu.
Paul B
PB
Samollow
D000818:Animals; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands; D019175:DNA Methylation; D005347:Fibroblasts / Q000378:metabolism*; D016678:Genome; D018392:Genomic Imprinting; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D008297:Male; D048309:Monodelphis / Q000235:genetics*; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D006657:Histones; D018398:Homeodomain Proteins; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins