Noncoding RNA genes in dosage compensation and imprinting.

摘要: Alleles silenced via imprinting are not thought to be packaged in densely compacted heterochromatin, but several imprinted genes have oppositely noncoding RNA partners nearby on the chromosome. Maternal expression of Igf2r gene is reminiscent Xist/Tsix locus that tied antisense transcription paternal chromosome (Wutz et al. 1997xWutz, A, Smrzka, O.W, Schweifer, N, Schellander, K, Wagner, E.F, and Barlow, D.P. Nature. 1997; 389: 745–749Crossref | PubMed Scopus (421)See all ReferencesWutz 1997) (Figure 1CFigure 1C). Perhaps most intensively studied example paternally expressed Ins2 Igf2 cluster linked maternally H19 (Tilghman 1999xTilghman, S.M. Cell. 1999; 96: 185–193Abstract Full Text PDF (385)See ReferencesTilghman 1999) 2AFigure 2A). Although no function has been found for RNA, it conserved abundantly expressed. Moreover, Dlk1/Gtl2 was recently a nearly identical arrangement protein coding adjacent suggesting some type selection these unusual RNAs (Schmidt 2000xSchmidt, J.V, Matteson, P.G, Jones, B.K, Guan, X.-J, Tilghman, Genes Dev. 2000; 14: 1997–2002PubMedSee ReferencesSchmidt 2000) 2BFigure 2B).Figure 2Reciprocal Imprinting Adjacent Protein-Coding Noncoding Genes(A) Reciprocal observed at where single enhancer drives either from homolog, or maternal The control region (ICR) contains CpG-rich sequences serve as binding site chromatin insulator CTCF. When CTCF occupies ICR, cannot act distal genes, transcribed. Paternal methylation ICR prevents allowing (5xHark, A.T, Schoenherr, C.J, Katz, D.J, Ingram, R.S, Levorse, J.M, 405: 486–489Crossref (946)See References, 3xBell, A.C Felsenfeld, G. 482–485Crossref (1003)See References).(B) Dlk1 upstream Gtl2 gene, which makes RNA. As with Igf2/H19 locus, differentially methylated (filled circle) lies gene.View Large Image View Hi-Res Download PowerPoint SlideAs unconventional being encountered novel epigenetic regulatory mechanisms, one striking feature synthesis critical function. In both mammals flies, moving Xist roX X autosomes redirects dosage compensation new sites insertion. Antisense Tsix homolog regulate allele other demonstrating exclusive cis activity. same appears true within locus. Is possible common regulator? By analogy discovered so far, could by repackaging local segment chromatin, capturing complementary mRNA, they simply by-products mutually action promoters.‡E-mail: rkelley@bcm.tmc.edu (R. L. K.), mkuroda@bcm.tmc.edu (M. I. K.)