Lashings of DNA methylation, forkfuls of chromatin remodeling

Meehan, Richard R.; Pennings, Sari; Stancheva, Irina

doi:10.1101/gad.954901

Cited by 34 publications

(22 citation statements)

References 45 publications

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“…More distantly related SNF2-like proteins, which are presumably the catalytic subunits of other ATPase remodeling complexes, have been shown to influence covalent histone modifications or DNA methylation (Gibbons et al 2000;Dennis et al 2001;Meehan et al 2001;Pray-Grant et al 2005). Less is known about Brg1 and SWI/SNF-related complexes in this regard, so we evaluated both types of epigenetic marks.…”

Section: Altered Histone Acetylation and Dna Methylation At The Lcrmentioning

confidence: 99%

A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in β-globin expression and erythroid development

Bultman¹,

Gebuhr²,

Magnuson³

2005

Genes Dev.

148

138

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The Brg1 catalytic subunit of SWI/SNF-related complexes has been implicated in many developmental and physiological processes, but null homozygotes die as blastocysts prior to implantation. To circumvent this early embryonic lethality, we performed an ENU mutagenesis screen and generated a Brg1 hypomorph mutation in the ATPase domain. The mutant Brg1 protein is stable, assembles into SWI/SNF-related complexes, and exhibits normal ATPase activity but is unable to establish DNase I hypersensitivity sites characteristic of open chromatin. Mutant embryos develop normally until midgestation but then exhibit a distinct block in the development of the erythroid lineage, leading to anemia and death. The mutant Brg1 protein is recruited to the ␤-globin locus, but chromatin remodeling and transcription are perturbed. Histone acetylation and DNA methylation are also affected. To our knowledge, Brg1 is the first chromatin-modifying factor shown to be required for ␤-globin regulation and erythropoiesis in vivo. Not only does this mutation establish a role for Brg1 during organogenesis, it also demonstrates that ATPase activity can be uncoupled from chromatin remodeling.[Keywords: ATPase; ␤ globin; Brg1; locus-control region; SWI/SNF; chromatin remodeling] Supplemental material is available at http://www.genesdev.org.

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Section: Altered Histone Acetylation and Dna Methylation At The Lcrmentioning

confidence: 99%

A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in β-globin expression and erythroid development

Bultman¹,

Gebuhr²,

Magnuson³

2005

Genes Dev.

148

138

View full text Add to dashboard Cite

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“…During subsequent cellular generations, this methylation is faithfully recapitulated by the action of the maintenance methyltransferase, DNMT1 (Li 2002). The linking of DNA methylation and histone deacetylation in specific genomic regions appears to confer a powerful mechanism for long-term gene silencing (Meehan et al 2001, Bird 2002, Sutherland & Costa 2003. It is emerging that the trigger for de novo methylation of DNA involves a series of histone modifications other than deacetylation, with methylation of histone H3 at the lysine 9 position (H3-K9) strongly correlating with DNA methylation (Felsenfeld & Groudine 2003, Jaenisch & Bird 2003.…”

mentioning

confidence: 99%

Epigenetics and the germline

Allegrucci¹,

Thurston²,

Lucas³

et al. 2005

Reproduction

198

125

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Epigenetic processes affect three stages of germline development, namely (1) specification and formation of primordial germ cells and their germline derivatives through lineage-specific epigenetic modifications, in the same manner as other embryonic lineages are formed, (2) a largely genome-wide erasure and re-establishment of germline-specific epigenetic modifications that only occurs in the embryonic primordial germ cell lineage, followed by re-establishment of sex-specific patterns during gametogenesis, and (3) differential epigenetic modifications to the mature male and female gamete genomes shortly after fertilisation. This review will detail current knowledge of these three processes both at the genome-wide level and at specific imprinted loci. The consequences of epigenetic perturbation are discussed and new in vitro models which may allow further understanding of a difficult developmental period to study, especially in the human, are highlighted.

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“…Few single copy genes affected by LSH deficiency have also been identified (Dennis et al 2001;Fan et al 2005;Xi et al 2007). It has been proposed that LSH remodels chromatin and thereby regulates the accessibility of DNA to de novo DNA methyltransferases DNMT3A and DNMT3B (Meehan et al 2001;Brzeski and Jerzmanowski 2003). LSH may also serve as a recruitment factor for DNMTs as it interacts with DNMT3A and DNMT3B and, indirectly via DNMT3B, with DNMT1 and histone deacetylases HDAC1 and HDAC2 (Zhu et al 2006;Myant and Stancheva 2008).…”

mentioning

confidence: 99%

“…One such protein is the putative chromatin remodeling ATPase LSH, also known as HELLS and PASG, encoded by the Hells gene. Initially identified as a factor required for proliferation of lymphoid cells, LSH is homologous to Arabidopsis thaliana Deficient in DNA Methylation 1 (DDM1) and closely related to the ISWI family of chromatin remodelers (Geiman and Muegge 2000;Dennis et al 2001;Meehan et al 2001). The LSH-null (Hells À/À ) mice lose up to 70% of 5-meC from their genome but survive through gestation and die soon after birth with reduced weight (Dennis et al 2001;Geiman et al 2001).…”

mentioning

confidence: 99%

LSH and G9a/GLP complex are required for developmentally programmed DNA methylation

Myant¹,

Termanis²,

Sundaram³

et al. 2010

Genome Res.

Self Cite

115

127

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LSH, a member of the SNF2 family of chromatin remodeling ATPases encoded by the Hells gene, is essential for normal levels of DNA methylation in the mammalian genome. While the role of LSH in the methylation of repetitive DNA sequences is well characterized, its contribution to the regulation of DNA methylation and the expression of proteincoding genes has not been studied in detail. In this report we investigate genome-wide patterns of DNA methylation at gene promoters in Hells -/-mouse embryonic fibroblasts (MEFs). We find that in the absence of LSH, DNA methylation is lost or significantly reduced at~20% of all normally methylated promoter sequences. As a consequence, a large number of genes are misexpressed in Hells -/-MEFs. Comparison of Hells -/-MEFs with wild-type MEFs and embryonic stem (ES) cells suggests that LSH is important for de novo DNA methylation events that accompany the establishment and differentiation of embryonic lineage cells. We further show that the generation of normal DNA methylation patterns and stable gene silencing at specific promoters require cooperation between LSH and the G9a/GLP complex of histone methylases. At such loci, G9a recruitment is compromised when LSH is absent or greatly reduced. Taken together, our data suggest a mechanism whereby LSH promotes binding of DNA methyltransferases and the G9a/GLP complex to specific loci and facilitates developmentally programmed DNA methylation and stable gene silencing during lineage commitment and differentiation.

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Lashings of DNA methylation, forkfuls of chromatin remodeling

Cited by 34 publications

References 45 publications

A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in β-globin expression and erythroid development

A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in β-globin expression and erythroid development

Epigenetics and the germline

LSH and G9a/GLP complex are required for developmentally programmed DNA methylation

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