Methylation and rearrangement of mouse intracisternal a particle genes in development, aging, and myeloma.

Mays-Hoopes, Laura L.; Brown, Anne Rain; Huang, Ru Chih C.

doi:10.1128/mcb.3.8.1371

Cited by 58 publications

(16 citation statements)

References 41 publications

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“…In the latter case, activation of transposable elements and endogenous retroviruses have been invoked and in some cases documented (35,36) as a possible event participating in somatic mutations. Along the same line, demethylation upon aging of the LINE murine mobile elements (and to some extent of the IAPs) has been reported (37,38). In fact, the present study (see also Refs.…”

Section: An Evolutionarily Conserved Orf With Similarity To the Yeastmentioning

confidence: 54%

Characterization of Two Age-induced Intracisternal A-particle-related Transcripts in the Mouse Liver

Puech

Dupressoír

Loireau

et al. 1997

Journal of Biological Chemistry

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Intracisternal A-particle (IAP) sequences are endogenous retrovirus-like elements present at 1,000 copies in the mouse genome. We had previously identified IAPrelated transcripts of unusual size (6 and 10 kilobases (kb)), which are observed exclusively in the liver of the aging mouse. In this report, using cDNA libraries that we have constructed from the liver mRNAs of an aged DBA/2 mouse, we have cloned and entirely sequenced the corresponding cDNAs. Both are initiated within the 5 long terminal repeat of a type I⌬1 IAP sequence, and correspond to a read-through into a unique flanking cellular sequence containing a 966-nucleotide open reading frame, located 3 to the IAP sequence. The 6-kb IAP-related transcript corresponds to a post-transcriptional modification of the 10-kb mRNA, and is generated by a splicing event with the donor site in the IAP sequence, and the acceptor site 5 to the open reading frame. This open reading frame is located on chromosome 3, is evolutionarily conserved, and discloses significant similarity to the yeast CCR4 transcription factor at the amino acid level. The specific expression of these age-induced transcripts, which account for more than 50% of the IAP-related transcripts in the liver of old mice, is therefore entirely consistent with the induction of a single genomic locus, thus strengthening the importance of position effects for the expression of transposable elements. Characterization of this locus should now allow studies on its chromatin and methylation status, and on the "molecular factors of senescence" possibly involved in its induction.

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Section: An Evolutionarily Conserved Orf With Similarity To the Yeastmentioning

confidence: 54%

Characterization of Two Age-induced Intracisternal A-particle-related Transcripts in the Mouse Liver

Puech

Dupressoír

Loireau

et al. 1997

Journal of Biological Chemistry

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“…There is some evidence that DNA methylation declines with age in vivo. Romanov and Vanyushin have demonstrated decreases in the methylation of reiterated, but not unique, sequences in cattle with ageing (24) whilst Mays-Hoopes et al have observed hypomethylation of specific moderately repeated sequences of the mouse liver genome with age (18). It is known that reiterated DNA sequences tend to have a higher proportion of methylated sites than other areas of the genome (21) and experiments are under way to look at keratinocyte reiterated DNA sequences in this regard.…”

Section: Discussionmentioning

confidence: 99%

In vitro senescence of human keratinocyte cultures.

Rockwell

Johnson

Sibatani

1987

Cell Struct. Funct.

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ABSTRACT. Human keratinocytes have been serially cultivated in low (0.015 mM) and high (1.8 mM) calcium containing medium. The calcium concentration of the growth medium significantly influenced the cell growth period in vitro. Cells grown in low calcium medium underwent 35-40 population doublings over 16-17 passages, while cells grown in high calcium medium ceased to proliferate after 20 population doublings over 7 passages. Changing the keratinocytes from one in vitro environment to the other drastically altered the lifespan in culture of populations derived from the same primary tissue. The degree of DNA methylation of human keratinocytes was shown to decrease with age in both high and low calcium culture conditions but does not appear to be associated with differentiation.

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“…In the present study, we have used a two-dimensional (2-D) gel electrophoresis technique to detect 1AP elements that are hypomethylated in their 5' long terminal repeats (LTRs). This approach is based on the observed correlation between the extent of 1AP proviral hypomethylation and the level of IAP expression in a number of cell lines (13)(14)(15)(16) (20 mA). By using a pulse controller (Hoefer PC750), the current was periodically reversed at a constant 3:1 ratio between the forward and reverse intervals; the reverse interval varied from 150 msec initially to 345 msec.…”

Section: Introductionmentioning

confidence: 99%

Tissue and strain-specific patterns of endogenous proviral hypomethylation analyzed by two-dimensional gel electrophoresis.

Mietz

Kuff

1990

Proc. Natl. Acad. Sci. U.S.A.

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Proviral sequences related to the intracisternal A particle (IAP) are amplified and dispersed in the mouse genome. Their expression is associated with hypomethylation at CpG sites in the 5' long terminal repeat. We have used two-dimensional agarose gel electrophoresis to examine patterns of LAP hypomethylation in mouse DNA. The method is sensitive to both the methylation status of a conserved Hae II site in the 5' long teiminal repeat and the location of the closest BamtII site in the flanking DNA upstream of each hypomethylated long terminal repeat. The method also detects restriction fragments derived from UAP elements that are themselves methylated but have an unmethylated Hae II site in their 5' adjacent DNA. DNAs from each of four inbred mouse strains (BALB/c, C3H/He, C57BL/6, and DBA/2) gave distinctive two-dimensional patterns of BamHl/Hae II restriction fragments detected by hybridization with an LAP probe. This constitutive pattern was largely conserved among several tissues of each strain, but some tissue-specific variations were observed. The site-specific hypomethylations reflected in the two-dimensional patterns were heritable properties, since DNA from progeny of an interstrain cross contained both parental sets of fragments. UAP elements may be useful endogenous reporters of genomic methylation patterns.DNA methylation is thought to have an important, perhaps determining, role in maintaining specific patterns of gene expression in eukaryotic cells (1, 2). In the genome, hypomethylated domains corresponding to active genetic loci are thought to be interspersed among regions of more heavily methylated inactive DNA. Major alterations in cell programming associated with normal differentiation or neoplastic transformation may involve widespread changes in patterns of DNA methylation (3, 4).Intracisternal A particles (lAPs) are defective retroviruses seen in many mouse tumors, in preimplantation embryos, and in certain normal tissues (reviewed in ref. 5). They are encoded by endogenous proviral elements, which are abundant (1000 copies per haploid genome) and distributed over the entire chromosome complement (6, 7). Transpositions of IAP elements have resulted in phenotypic alterations, such as loss of immunoglobulin light chain expression (8), constitutive oncogene activation (9), and growth factor production (10, 11). Although intracisternal expression has no apparent consequence for the producing cell, particle proteins that gain access to the cell exterior can behave as neoantigens (12).These IAP-associated effects could be related to the expression of particular proviral elements that are transposition-prone or encode strongly antigenic variants of IAP proteins. However, detection of individual active IAP elements has been difficult because of the large number of homologous copies. In the present study, we have used a two-dimensional (2-D) gel electrophoresis technique to detect 1AP elements that are hypomethylated in their 5' long terminal repeats (LTRs). This approach is based on the obse...

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Methylation and rearrangement of mouse intracisternal a particle genes in development, aging, and myeloma.

Cited by 58 publications

References 41 publications

Characterization of Two Age-induced Intracisternal A-particle-related Transcripts in the Mouse Liver

Characterization of Two Age-induced Intracisternal A-particle-related Transcripts in the Mouse Liver

In vitro senescence of human keratinocyte cultures.

Tissue and strain-specific patterns of endogenous proviral hypomethylation analyzed by two-dimensional gel electrophoresis.

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