MrgX is not essential for cell growth and development in the mouse.
MRGX is one of the members of MORF4/MRG family of transcriptional regulators, which are involved in cell growth regulation and cellular senescence. We have shown that MRGX and MRG15 associate with Rb in nucleoprotein complexes and regulate B-myb promoter activity. To elucidate the functions of MRGX and to explore its potential role in modulating cell growth in vivo, we have generated MrgX-deficient mice. Characterization of the expression pattern of mouse MrgX demonstrated it was ubiquitously expressed in all tissues of adult mice and also during embryogenesis and overlapped with its homolog Mrg15. MRGX and MRG15 proteins localize predominantly to the chromatin fraction in the nucleus, although a small amount of both proteins localized to the nuclear matrix. Whereas disruption of Mrg15 results in embryonic lethality, absence of MrgX did not impair mouse development and MrgX null mice are healthy and fertile. MrgX-deficient and wild-type mouse embryonic fibroblasts (MEFs) also had similar growth rates and showed no differences in cell cycle-related gene expression in response to serum stimulation. Mrg15 expression in MrgX-deficient tissues and MEFs was not upregulated compared with wild-type tissues and MEFs. MRG15 is highly conserved with orthologs present from humans to yeast and is essential for survival of mice. In contrast, MRGX, which evolved later, is expressed only in vertebrates, suggesting that the lack of phenotype of MrgX-deficient mice is secondary to a compensatory effect by the evolutionarily conserved MRG15 protein but not vice versa.
Tominaga
Kaoru
K
Sam and Ann Barshop Institute for Longevity and Aging Studies, Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245-3207, USA. tominaga@uthscsa.edu
Matzuk
Martin M
MM
Pereira-Smith
Olivia M
OM
D000818:Animals; D002458:Cell Fractionation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology*; D047108:Embryonic Development; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D018816:Genes, cdc; D005838:Genotype; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C491669:MORF4L2 protein, human; C471162:MRG15 protein, mouse; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D015534:Trans-Activators; D014157:Transcription Factors