Long-range DNase I hypersensitivity mapping reveals the imprinted Igf2r and Air promoters share cis-regulatory elements

Pauler, Florian M.; Stricker, Stefan H.; Warczok, Katarzyna E.; Barlow, Denise P.

doi:10.1101/gr.3783805

Cited by 30 publications

(27 citation statements)

References 45 publications

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“…It is noteworthy that Airn and Igf2r show similar expression kinetics in mouse tissues and differentiated ESCs (Latos et al, 2009;Pauler et al, 2005). This could indicate that Airn repressor activity is limited by higher Igf2r promoter activity.…”

Section: Airn Expression Can Silence Igf2r At Any Time During Esc Difmentioning

confidence: 78%

Imprinted Igf2r silencing depends on continuous Airn lncRNA expression and is not restricted to a developmental window

et al. 2013

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The imprinted Airn macro long non-coding (lnc) RNA is an established example of a cis-silencing lncRNA. Airn expression is necessary to initiate paternal-specific silencing of the Igf2r gene, which is followed by gain of a somatic DNA methylation imprint on the silent Igf2r promoter. However, the developmental requirements for Airn initiation of Igf2r silencing and the role of Airn or DNA methylation in maintaining stable Igf2r repression have not been investigated. Here, we use inducible systems to control Airn expression during mouse embryonic stem cell (ESC) differentiation. By turning Airn expression off during ESC differentiation, we show that continuous Airn expression is needed to maintain Igf2r silencing, but only until the paternal Igf2r promoter is methylated. By conditionally turning Airn expression on, we show that Airn initiation of Igf2r silencing is not limited to one developmental ‘window of opportunity’ and can be maintained in the absence of DNA methylation. Together, this study shows that Airn expression is both necessary and sufficient to silence Igf2r throughout ESC differentiation and that the somatic methylation imprint, although not required to initiate or maintain silencing, adds a secondary layer of repressive epigenetic information.

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Section: Airn Expression Can Silence Igf2r At Any Time During Esc Difmentioning

confidence: 78%

Imprinted Igf2r silencing depends on continuous Airn lncRNA expression and is not restricted to a developmental window

et al. 2013

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“…The active promoters of Igf2r , SNRPN , Nesp , GnasXL and Air, Nespas and Kcnq1ot1 are associated with parentalspecifi c DHS sites. No DHS sites are detected around the inactive methylated promoters of these genes (Schweizer et al, 1999;Coombes et al, 2003;Mancini-DiNardo et al, 2003;Pauler et al, 2005). At the Igf2/H19 paternal imprinting system, a DHS site is present at the active, unmethylated but not at the inactive, methylated promoter of the H19 gene (Khosla et al, 1999).…”

Section: Nucleosome Densitymentioning

confidence: 84%

The imprinted mouse Igf2r/Air cluster – a model maternal imprinting system

Regha

Latos

Spahn

2006

Cytogenet Genome Res

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Every diploid organism inherits a complete chromosome set from its father and mother in addition to the sex chromosomes, so that all autosomal genes are available in two copies. For most genes, both copies are expressed without preference. Imprinted genes, however, are expressed depending on their parental origin, being active on the paternal or maternal allele only. To date 73 imprinted genes are known in mouse (www.mgu.har.mrc.ac.uk/research/imprinting), 37 show paternal expression while 36 show maternal expression, indicating no bias for imprinting to occur in one sex or the other. Therefore, two different parental-specific imprinting systems may have evolved in mammals, acting specifically in the paternal or maternal gamete. Similarities and differences between the two imprinting systems will be reviewed, with specific reference to the role of non-coding RNAs and chromatin modifications. The mouse Igf2r/Air cluster is presented as a model of the maternal imprinting system.

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“…It is also possible for 3′-3′ or fully overlapped transcripts to compete for or share common transcriptional factor binding sites, since genomic regions harboring regulatory elements can stretch as much as 1 Mb in either direction from the transcription unit [136]. For example, results from DNase I footprinting suggest that imprinted Igf2R and Air promoters appear to share common cis-regulatory elements [137]. In addition, one recent genome-scale study showed that about 4% of CREB binding sites are located at the 3′ end of the target genes, many of which have known antisense transcripts [138].…”

Section: Class I Model: Transcriptional Regulation Independent Of Ovementioning

confidence: 99%

Overlapping transcripts, double-stranded RNA and antisense regulation: A genomic perspective

Munroe

Zhu

2006

Cell. Mol. Life Sci.

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Bioinformatic analysis of the transcriptomes of diverse eukaryotes has demonstrated the ubiquity and structural diversity of complementary antisense RNAs. These include both trans-encoded microRNAs and a large population of cis-encoded antisense RNAs that encompasses both coding and non-coding RNAs. Antisense regulation has previously been characterized primarily as a post-transcriptional response affecting RNA stability, nuclear processing, export, or translation. However, the formation of double-stranded (ds) RNAs by base-pairing between complementary RNAs may elicit regulatory responses at the transcriptional level as well. Analysis of antisense transcription at several imprinted loci has suggested a number of other mechanisms that may not require formation of dsRNA. Understanding the integration of transcriptional and post-transcriptional regulatory mechanisms represents a major challenge for understanding antisense regulation in eukaryotes. Such insight is also essential for understanding general principles of genetic regulation within the complex genomes characteristic of mouse and man as well as those of other eukaryotes.

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Long-range DNase I hypersensitivity mapping reveals the imprinted Igf2r and Air promoters share cis-regulatory elements

Cited by 30 publications

References 45 publications

Imprinted Igf2r silencing depends on continuous Airn lncRNA expression and is not restricted to a developmental window

Imprinted Igf2r silencing depends on continuous Airn lncRNA expression and is not restricted to a developmental window

The imprinted mouse <i>Igf2r/Air</i> cluster – a model maternal imprinting system

Overlapping transcripts, double-stranded RNA and antisense regulation: A genomic perspective

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