Step-Wise Methylation of Histone H3K9 Positions Heterochromatin at the Nuclear Periphery

Towbin, Benjamin D.; González-Aguilera, Cristina; Sack, Ragna; Gaidatzis, Dimos; Kalck, Véronique; Meister, Peter; Askjaer, Peter; Gasser, Susan M.

doi:10.1016/j.cell.2012.06.051

Cited by 522 publications

(814 citation statements)

References 55 publications

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“…Conversion of H3K9me2 to H3K9me3 is most likely mediated by the joint action of Cbr-MES-2 and Cbr-SET-25, and perhaps additional histone methyltransferases (Figure 4). While MES-2 is important for generation of H3K9me3 in the C. elegans germ line (Bessler et al 2010), SET-25 has been shown to be important for acquisition of H3K9me3 in the C. elegans embryo (Towbin et al 2012). We found that RNAi inactivation of SET-25 in C. elegans results in accumulation of H3K9me2 in the germ line ( Figure S4), indicating Cel-SET-25 also functions in the germ line as suggested by Ashe et al (2012).…”

Section: H3k9me2 Vs H3k9me3mentioning

confidence: 62%

“…To distinguish between these possibilities, we depleted the methyltransferases Cbr-MES-2 and Cbr-SET-25, which mediate the conversion of H3K9me2 to H3K9me3 in C. elegans germ cells and embryos, respectively (Bessler et al 2010;Towbin et al 2012). Furthermore, inactivation of Cel-set-25 by RNAi revealed elevated levels of germ-line H3K9me2, indicating that SET-25 also functions in the C. elegans germ line to convert H3K9me2 to H3K9me3 ( Figure S4A).…”

Section: The X Chromosome Of Males Is Enriched For Different Repressimentioning

confidence: 99%

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Plasticity in the Meiotic Epigenetic Landscape of Sex Chromosomes inCaenorhabditisSpecies

Larson

Van

Nakayama³

et al. 2016

Genetics

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During meiosis in the heterogametic sex in some species, sex chromosomes undergo meiotic sex chromosome inactivation (MSCI), which results in acquisition of repressive chromatin and transcriptional silencing. In Caenorhabditis elegans, MSCI is mediated by MET-2 methyltransferase deposition of histone H3 lysine 9 dimethylation. Here we examined the meiotic chromatin landscape in germ lines of four Caenorhabditis species; C. remanei and C. brenneri represent ancestral gonochorism, while C. briggsae and C. elegans are two lineages that independently evolved hermaphroditism. While MSCI is conserved across all four species, repressive chromatin modifications are distinct and do not correlate with reproductive mode. In contrast to C. elegans and C. remanei germ cells where X chromosomes are enriched for histone H3 lysine 9 dimethylation, X chromosomes in C. briggsae and C. brenneri germ cells are enriched for histone H3 lysine 9 trimethylation. Inactivation of C. briggsae MET-2 resulted in germ-line X chromosome transcription and checkpoint activation. Further, both histone H3 lysine 9 di-and trimethylation were reduced in Cbr-met-2 mutant germ lines, suggesting that in contrast to C. elegans, H3 lysine 9 di-and trimethylation are interdependent. C. briggsae H3 lysine 9 trimethylation was redistributed in the presence of asynapsed chromosomes in a sex-specific manner in the related process of meiotic silencing of unsynapsed chromatin. However, these repressive marks did not influence X chromosome replication timing. Examination of additional Caenorhabditis species revealed diverse H3 lysine 9 methylation patterns on the X, suggesting that the sex chromosome epigenome evolves rapidly.

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Section: H3k9me2 Vs H3k9me3mentioning

confidence: 62%

Section: The X Chromosome Of Males Is Enriched For Different Repressimentioning

confidence: 99%

Plasticity in the Meiotic Epigenetic Landscape of Sex Chromosomes inCaenorhabditisSpecies

Larson

Van

Nakayama³

et al. 2016

Genetics

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“…We therefore tested whether predicted H3K9 histone methyltransferases (HMTases) and potential interactors of HPL-2 also play a role in the ER stress response. Two HMTases, SET-25 and MET-2, are required for H3K9me in C. elegans (25,26). Whereas animals lacking set-25 showed a wild-type response to ER stress, animals lacking met-2 showed enhanced resistance (Fig.…”

Section: Hpl-2 Acts In the Same Pathway As The Rb Homolog Lin-35 And Thementioning

confidence: 99%

The Caenorhabditis elegans HP1 family protein HPL-2 maintains ER homeostasis through the UPR and hormesis

Kozlowski

Garvis

Bedet

et al. 2014

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

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Cellular adaptation to environmental changes and stress relies on a wide range of regulatory mechanisms that are tightly controlled at several levels, including transcription. Chromatin structure and chromatin binding proteins are important factors contributing to the transcriptional response to stress. However, it remains largely unknown to what extent specific chromatin factors influence the response to distinct forms of stress in a developmental context. One of the best characterized stress response pathways is the unfolded protein response (UPR), which is activated by accumulation of misfolded proteins in the endoplasmic reticulum (ER). Here, we show that Caenorhabditis elegans heterochromatin protein like-2 (HPL-2), the homolog of heterochromatin protein 1 (HP1), downregulates the UPR in the intestine. Inactivation of HPL-2 results in an enhanced resistance to ER stress dependent on the X-box binding protein 1 (XBP-1)/inositol requiring enzyme 1 branch of the UPR and the closely related process of autophagy. Increased resistance to ER stress in animals lacking HPL-2 is associated with increased basal levels of XBP-1 activation and ER chaperone expression under physiological conditions, which may in turn activate an adaptive response known as ER hormesis. HPL-2 expression in intestinal cells is sufficient to rescue stress resistance, whereas expression in neuronal cells negatively influenced the ER stress response through a cell-nonautonomous mechanism. We further show that the retinoblastoma protein homolog LIN-35 and the LIN-13 zinc finger protein act in the same pathway as HPL-2 to limit the ER stress response. Altogether, our results point to multiple functions for HP1 in different cell types to maintain ER homeostasis.

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“…LADs have initially been discovered by DamID (DNA adenine methyltransferase [Dam] identification, a proximity assay). 2 Features of LADs include residence in overall transcriptionally silent heterochromatin 2,9 consistent with enrichment of this compartment at the nuclear periphery, 5,10,11 and a gene-poor content. 2 Large chromatin domains with similar properties have also been identified by chromatin immunoprecipitation (ChIP) of lamin A/C (referred to here as LMNA) or lamin B1 (LMNB1) coupled to array hybridization 12 or highthroughput sequencing (ChIP-seq).…”

Section: Introductionmentioning

confidence: 99%

Distinct features of lamin A-interacting chromatin domains mapped by ChIP-sequencing from sonicated or micrococcal nuclease-digested chromatin

Lund

Duband-Goulet

Oldenburg

et al. 2015

Nucleus

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The nuclear lamina has been shown to interact with the genome through lamina-associated domains (LADs). LADs have been identified by DamID, a proximity labeling assay, and more recently by chromatin immunoprecipitationsequencing (ChIP-seq) of A-and B-type lamins. LADs form megabase-size domains at the nuclear periphery, they are gene-poor and mostly heterochromatic. Here, we show that the mode of chromatin fragmentation for ChIP, namely bath sonication or digestion with micrococcal nuclease (MNase), leads to the discovery of common but also distinct sets of lamin-interacting domains, or LiDs. Using ChIP-seq, we show the existence of lamin A/C (LMNA) LiDs with distinct gene contents, histone composition enrichment and relationships to lamin B1-interacting domains. The extent of genome coverage of lamin A/C (LMNA) LiDs in sonicated or MNase-digested chromatin is similar (»730 megabases); however over half of these domains are uniquely detected in sonicated or MNase-digested chromatin. Sonicationspecific LMNA LiDs are gene-poor and devoid of a broad panel of histone modifications, while MNase-specific LMNA LiDs are of higher gene density and are enriched in H3K9me3, H3K27me3 and in histone variant H2A.Z. LMNB1 LiDs are gene-poor and show no or little enrichment in these marks. Comparison of published LMNB1 DamID LADs with LMNB1 and LMNA LiDs identified here by ChIP-seq further shows that LMNA can associate with 'open' chromatin domains displaying euchromatin characteristics, and which are not associated with LMNB1. The differential genomic and epigenetic properties of lamin-interacting domains reflect the existence of distinct LiD populations identifiable in different chromatin contexts, including nuclease-accessible regions presumably localized in the nuclear interior.

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Step-Wise Methylation of Histone H3K9 Positions Heterochromatin at the Nuclear Periphery

Cited by 522 publications

References 55 publications

Plasticity in the Meiotic Epigenetic Landscape of Sex Chromosomes inCaenorhabditisSpecies

Plasticity in the Meiotic Epigenetic Landscape of Sex Chromosomes inCaenorhabditisSpecies

The Caenorhabditis elegans HP1 family protein HPL-2 maintains ER homeostasis through the UPR and hormesis

Distinct features of lamin A-interacting chromatin domains mapped by ChIP-sequencing from sonicated or micrococcal nuclease-digested chromatin

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