MRG15 regulates embryonic development and cell proliferation.
MRG15 is a highly conserved protein, and orthologs exist in organisms from yeast to humans. MRG15 associates with at least two nucleoprotein complexes that include histone acetyltransferases and/or histone deacetylases, suggesting it is involved in chromatin remodeling. To study the role of MRG15 in vivo, we generated knockout mice and determined that the phenotype is embryonic lethal, with embryos and the few stillborn pups exhibiting developmental delay. Immunohistochemical analysis indicates that apoptosis in Mrg15-/- embryos is not increased compared with wild-type littermates. However, the number of proliferating cells is significantly reduced in various tissues of the smaller null embryos compared with control littermates. Cell proliferation defects are also observed in Mrg15-/- mouse embryonic fibroblasts. The hearts of the Mrg15-/- embryos exhibit some features of hypertrophic cardiomyopathy. The increase in size of the cardiomyocytes is most likely a response to decreased growth of the cells. Mrg15-/- embryos appeared pale, and microarray analysis revealed that alpha-globin gene expression was decreased in null versus wild-type embryos. We determined by chromatin immunoprecipitation that MRG15 was recruited to the alpha-globin promoter during dimethyl sulfoxide-induced mouse erythroleukemia cell differentiation. These findings demonstrate that MRG15 has an essential role in embryonic development via chromatin remodeling and transcriptional regulation.
Tominaga
Kaoru
K
Department of Cellular and Structural Biology, Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245-3207, USA. tominaga@uthscsa.edu
Kirtane
Bhakti
B
Jackson
James G
JG
Ikeno
Yuji
Y
Ikeda
Takayoshi
T
Hawks
Christina
C
Smith
James R
JR
Matzuk
Martin M
MM
Pereira-Smith
Olivia M
OM
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D006332:Cardiomegaly / Q000209:etiology; D002453:Cell Cycle; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D047108:Embryonic Development / Q000235:genetics*; D017353:Gene Deletion; D018390:Gene Targeting; D005804:Genes, Lethal; D005914:Globins / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000196:embryology; D008168:Lung / Q000196:embryology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology; D011401:Promoter Regions, Genetic; D014018:Tissue Distribution; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C471162:MRG15 protein, mouse; D015534:Trans-Activators; D005914:Globins