Maternal inhibition of hepatitis B surface antigen gene expression in transgenic mice correlates with de novo methylation

Hadchouel, Michelle; Farza, Hend; Simon, Dominique; Tiollais, Pierre; Pourcel, Christine

doi:10.1038/329454a0

Cited by 185 publications

(81 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our data differ from the reported success of therapeutic vaccination with HBsAgencoding expression plasmid DNA in a different HBs-tg lineage (31,43,44). The reported successful therapeutic vaccination in this system might be related to the fact that HBsAg transgene expression in this particular lineage is extinguished by methylation (45)(46)(47)(48). It is unlikely that a deficient anti-pre-S immunity was critical for the failure of our therapeutic vaccination.…”

Section: Unsuccessful Vaccination Of Tg Micecontrasting

confidence: 55%

Ongoing Murine T1 or T2 Immune Responses to the Hepatitis B Surface Antigen Are Excluded from the Liver that Expresses Transgene-Encoded Hepatitis B Surface Antigen

Schirmbeck

Wild

Stober

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

Different protein- or DNA-based vaccination techniques are available that prime potent humoral and cellular, T1 or T2 immune responses to the hepatitis B surface Ag (HBsAg) in mice. T1 and T2 are immune responses with isotype profile indicating Th1 and Th2 immunoregulation. We tested whether HBsAg-specific immune responses can be established in transgenic mice that express HBsAg in the liver (HBs-tg mice) using either these different vaccination techniques or an adoptive transfer system. HBsAg-specific responses could not be primed in HBs-tg mice with the established, potent vaccine delivery techniques. In contrast, adoptive transfers of T1- and T2-type HBsAg-immune spleen cells into congenic HBs-tg hosts (that were not conditioned by pretreatment) suppressed HBsAg antigenemia and gave rise to HBsAg-specific serum Ab titers. The establishment of continuously rising anti-HBsAg serum Ab levels with alternative isotype profiles (reflecting T1 or T2 polarization) in transplanted HBs-tg hosts required donor CD4+ T cell-dependent restimulation of adoptively transferred immune cells by transgene-derived HBsAg. Injections of HBsAg-specific Abs into HBs-tg mice did not establish stable humoral immunity. The expanding T1 or T2 immune responses to HBsAg in HBs-tg hosts did not suppress transgene-directed HBsAg expression in the liver and did not induce liver injury. In addition to priming functional antiviral effector cells, the conditioning of the liver microenvironment to enable delivery of antiviral effector functions to this organ are therefore critical for effective antiviral defense. A major challenge in the development of a therapeutic vaccine against chronic hepatitis B or C virus infection is thus the efficient targeting of specifically induced immune effector specificities to the liver.

show abstract

Section: Unsuccessful Vaccination Of Tg Micecontrasting

confidence: 55%

Ongoing Murine T1 or T2 Immune Responses to the Hepatitis B Surface Antigen Are Excluded from the Liver that Expresses Transgene-Encoded Hepatitis B Surface Antigen

Schirmbeck

Wild

Stober

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…This imprinting was independent of the genetic background in which it was measured, as the imprinting was observed in both progeny outcrossed to CD1 mice, as well as mice that had been inbred for three generations into DBA/2J (data not shown). Thus, the imprinting cannot be explained by the presence of a single dominant genetic modifier, as has been observed for other transgenes (Hadchouel et al 1987;Sapienza et al 1989;Allen et al 1990;Engler et al 1991), although the presence of complex genetic modifications cannot be ruled out until the transgenes are on completely inbred backgrounds. The appropriate imprinting of the H19 transgene confirms that the elements required for its allele-specific expression are localized to a small region surrounding the structural gene.…”

Section: Discussionmentioning

confidence: 99%

“…The silent maternally inherited copies were highly methylated. Since then, additional examples have been reported, all but one of which is maternally methylated (Hadchouel et al 1987;Reik et al 1987;Sapienza et al 1987;Sasaki et al 1991;Ueda et al 1992).…”

Section: Discussionmentioning

confidence: 99%

“…This covalent modification of DNA has been implicated in the perpetuation of the imprinting state in X chromosome inactivation, on the basis of the observation that genes on the inactive X chromosome are more highly methylated than their counterparts on the active X (for review, see Riggs and Pfeifer 1992). In addition a set of transgenes in mice exhibit parent-of-origin differences in DNA methylation, and in at least one instance, the methylation acts to silence the expression of the transgene (Hadchouel et al 1987;Reik et al 1987;Sapienza et al 1987;Swain et al 1987;Chafflet et al 1991;Sasaki et al 1991;Ueda et al 1992). In all but one of these transgenic mouse lines, the transgene becomes methylated after passage through the female germline.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Epigenetic mechanisms underlying the imprinting of the mouse H19 gene.

Bartolomei¹,

Webber²,

Brunkow³

et al. 1993

Genes Dev.

458

328

View full text Add to dashboard Cite

The expression of the H19 gene is governed by parental imprinting in mammals. H19, an unusual gene encoding an RNA with no known function, is exclusively expressed from the maternal chromosome. In mouse, it lies 90 kb downstream from the lgf2 gene, which encodes a fetal-specific growth factor, insulin-like growth factor II, and is expressed primarily from the paternally inherited chromosome. In this report we have utilized interspecific hybrid mice to identify male-specific DNA methylation of a 7-to 9-kb domain surrounding the 1-119 gene and its promoter. This allele-specific methylation could function as a mark to suppress transcription of the H19 paternal allele. Consistent with this proposal, the H19 promoter displayed an open chromatin conformation only on the relatively unmethylated active maternal allele. In contrast, a cell type-specific enhancer that lies outside the methylation domain is hypersensitive to restriction enzyme digestion in nuclei on both maternal and paternal chromosomes. That the allele-specific methylation domain, coupled to the two H19 enhancers, contains all the information necessary for its imprinting was tested by examining two transgenic lines containing an internally deleted H19 transgene. Both displayed paternal-specific methylation of the transgene and maternal-specific expression. Although neither line has been tested in an inbred genetic background, and therefore the action of complex modifiers cannot be formally excluded, the result suggests that the sequences necessary for the imprinting of H19 have been identified.

show abstract

“…For instance, it has been shown to affect tissue specific gene regulation, parental imprinting, and X-inactivation (for reviews, see Busslinger et al, 1983;Cedar, 1988;Lyon, 1988;Weissbach et al, 1989). Studies on both transferred genes (Busslinger et al, 1983;Hadchouel et al, 1987;Ledent et al, 1990;Rimoldi et al, 1991) and endogenous genes (Stein et al, 1983;Hansen and Gartler, 1990) have shown a correlation between 0 1994 WILEY-LISS, INC. specific methylation patterns of DNA sequences and the status of specific gene expression. Further evidence for this relationship comes from studies employing a DNA methylation inhibitor, 5-azacytidine (5-AzaC) (Glover and Leyland-Jone, 19871, in both animals and cultured cells.…”

mentioning

confidence: 99%

Demethylation in the 5′‐flanking region of mouse cellular retinoic acid binding protein‐I gene is associated with its high level of expression in mouse embryos and facilitates its induction by retinoic acid in P19 embryonal carcinoma cells

Wei

Lee

1994

Developmental Dynamics

View full text Add to dashboard Cite

The mouse cellular retinoic acid binding protein-I (CRABP-I) gene is specifically up-regulated by retinoic acid (RA) in P19 mouse embryonal carcinoma cells, and its expression in animals is spatially and temporally restricted to RA-sensitive tissues during embryonic development. This study demonstrates that, in adult mouse tissues and P19 cells where the expression of CRABP-I is detected at the basal level, the 5'-flanking region of the CRABP-I gene is hypermethylated at the C residues of all the H p a I1 sites. Conversely, in mouse embryos during early stages of development when the expression of CRABP-I gene is detected at a much higher level, this region is demethylated at these H p a I1 sites. In P19, enhancement on the RA-induced up-regulation of CRABP-I can be observed in cells treated with 5-azacytidine (5-AzaC) in conjunction with RA, where partial demethylation in the 5'-flanking region of CRABP-I gene is observed. Nuclear run-on experiments indicate that increased message levels of CRABP-I in P19 cells can be accounted for, at least partially, by increases in its transcription rates. The induction of retinoic acid receptor (RAR) p by RA can also be enhanced by 5-AzaC, but to a much lesser degree. In contrast, all the H p a I1 sites in the structural gene portion, at least in the first two exons, are fully demethylated at the C residues. o 1994 WiIey-Liss, Inc.

show abstract

Maternal inhibition of hepatitis B surface antigen gene expression in transgenic mice correlates with de novo methylation

Cited by 185 publications

References 13 publications

Ongoing Murine T1 or T2 Immune Responses to the Hepatitis B Surface Antigen Are Excluded from the Liver that Expresses Transgene-Encoded Hepatitis B Surface Antigen

Ongoing Murine T1 or T2 Immune Responses to the Hepatitis B Surface Antigen Are Excluded from the Liver that Expresses Transgene-Encoded Hepatitis B Surface Antigen

Epigenetic mechanisms underlying the imprinting of the mouse H19 gene.

Demethylation in the 5′‐flanking region of mouse cellular retinoic acid binding protein‐I gene is associated with its high level of expression in mouse embryos and facilitates its induction by retinoic acid in P19 embryonal carcinoma cells

Contact Info

Product

Resources

About