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Chromatin states and nuclear organization in development--a view from the nuclear lamina.

Mattout A, Cabianca DS, Gasser SM - Genome Biol. (2015)

Bottom Line: The spatial distribution of chromatin domains in interphase nuclei changes dramatically during development in multicellular organisms.A crucial question is whether nuclear organization is a cause or a result of differentiation.Genetic perturbation of lamina-heterochromatin interactions is helping to reveal the cross-talk between chromatin states and nuclear organization.

View Article: PubMed Central - PubMed

Affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058, Basel, Switzerland. anna.mattout@fmi.ch.

ABSTRACT
The spatial distribution of chromatin domains in interphase nuclei changes dramatically during development in multicellular organisms. A crucial question is whether nuclear organization is a cause or a result of differentiation. Genetic perturbation of lamina-heterochromatin interactions is helping to reveal the cross-talk between chromatin states and nuclear organization.

No MeSH data available.


Related in: MedlinePlus

Histone modifications regulate perinuclear sequestration. A model of known and suggested histone tail modifications involved in heterochromatin anchoring at the nuclear envelope. The deposition of histones carrying H3K9me1 or H3K9me2 could be sufficient to ensure localization at the nuclear envelope according to work with the worm Caenorhabditis elegans [74]. Potential methyl readers that might contribute to anchoring include the lamin B receptor (LBR) in mammals and a C. elegans chromodomain protein (CEC-x) in worms. Readers of the H3K9me3 modification that ensure silencing include worm homologs of heterochromatin protein 1 (HP1) and LIN-61. Other factors implicated in tissue-specific gene repression and sequestration include cKROX and HDAC3, or an unknown reader of H4K20me3. See text for further details
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Fig2: Histone modifications regulate perinuclear sequestration. A model of known and suggested histone tail modifications involved in heterochromatin anchoring at the nuclear envelope. The deposition of histones carrying H3K9me1 or H3K9me2 could be sufficient to ensure localization at the nuclear envelope according to work with the worm Caenorhabditis elegans [74]. Potential methyl readers that might contribute to anchoring include the lamin B receptor (LBR) in mammals and a C. elegans chromodomain protein (CEC-x) in worms. Readers of the H3K9me3 modification that ensure silencing include worm homologs of heterochromatin protein 1 (HP1) and LIN-61. Other factors implicated in tissue-specific gene repression and sequestration include cKROX and HDAC3, or an unknown reader of H4K20me3. See text for further details

Mentions: To go beyond a simple correlation of H3K9 methylation and heterochromatin anchoring, genetic approaches are needed. The most extensive screen for factors involved in sequestering chromatin at the NE was a genome-wide RNA interference (RNAi) screen in C. elegans [74]. Using an integrated heterochromatic reporter, the Gasser laboratory identified two HMTs — MET-2 and SET-25 — as essential factors for the anchoring of heterochromatin to the NE in embryos. The first enzyme, MET-2, is the homolog of the mammalian histone-lysine N-methyltransferase SETDB1 (ESET), whereas SET-25 has a SET domain very similar to that of histone-lysine N-methyltransferase G9a (EHMT2), but lacks homology outside this region [74]. MET-2 and SET-25 work in a stepwise fashion, exclusively modifying histone H3K9 by depositing mono- (MET-2), di- (MET-2) and tri-methylation (SET-25). The met-2 set-25 double-mutants lack all H3K9 methylation in embryos and during somatic cell differentiation, which not only de-represses a heterochromatic reporter but releases both it and endogenous H3K9me-enriched chromatin from the nuclear periphery, as mapped by lamin-DamID [71, 74] (Fig. 2). This links H3K9 methylation causally to chromatin anchoring, at least in early worm development.Fig. 2


Chromatin states and nuclear organization in development--a view from the nuclear lamina.

Mattout A, Cabianca DS, Gasser SM - Genome Biol. (2015)

Histone modifications regulate perinuclear sequestration. A model of known and suggested histone tail modifications involved in heterochromatin anchoring at the nuclear envelope. The deposition of histones carrying H3K9me1 or H3K9me2 could be sufficient to ensure localization at the nuclear envelope according to work with the worm Caenorhabditis elegans [74]. Potential methyl readers that might contribute to anchoring include the lamin B receptor (LBR) in mammals and a C. elegans chromodomain protein (CEC-x) in worms. Readers of the H3K9me3 modification that ensure silencing include worm homologs of heterochromatin protein 1 (HP1) and LIN-61. Other factors implicated in tissue-specific gene repression and sequestration include cKROX and HDAC3, or an unknown reader of H4K20me3. See text for further details
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4549078&req=5

Fig2: Histone modifications regulate perinuclear sequestration. A model of known and suggested histone tail modifications involved in heterochromatin anchoring at the nuclear envelope. The deposition of histones carrying H3K9me1 or H3K9me2 could be sufficient to ensure localization at the nuclear envelope according to work with the worm Caenorhabditis elegans [74]. Potential methyl readers that might contribute to anchoring include the lamin B receptor (LBR) in mammals and a C. elegans chromodomain protein (CEC-x) in worms. Readers of the H3K9me3 modification that ensure silencing include worm homologs of heterochromatin protein 1 (HP1) and LIN-61. Other factors implicated in tissue-specific gene repression and sequestration include cKROX and HDAC3, or an unknown reader of H4K20me3. See text for further details
Mentions: To go beyond a simple correlation of H3K9 methylation and heterochromatin anchoring, genetic approaches are needed. The most extensive screen for factors involved in sequestering chromatin at the NE was a genome-wide RNA interference (RNAi) screen in C. elegans [74]. Using an integrated heterochromatic reporter, the Gasser laboratory identified two HMTs — MET-2 and SET-25 — as essential factors for the anchoring of heterochromatin to the NE in embryos. The first enzyme, MET-2, is the homolog of the mammalian histone-lysine N-methyltransferase SETDB1 (ESET), whereas SET-25 has a SET domain very similar to that of histone-lysine N-methyltransferase G9a (EHMT2), but lacks homology outside this region [74]. MET-2 and SET-25 work in a stepwise fashion, exclusively modifying histone H3K9 by depositing mono- (MET-2), di- (MET-2) and tri-methylation (SET-25). The met-2 set-25 double-mutants lack all H3K9 methylation in embryos and during somatic cell differentiation, which not only de-represses a heterochromatic reporter but releases both it and endogenous H3K9me-enriched chromatin from the nuclear periphery, as mapped by lamin-DamID [71, 74] (Fig. 2). This links H3K9 methylation causally to chromatin anchoring, at least in early worm development.Fig. 2

Bottom Line: The spatial distribution of chromatin domains in interphase nuclei changes dramatically during development in multicellular organisms.A crucial question is whether nuclear organization is a cause or a result of differentiation.Genetic perturbation of lamina-heterochromatin interactions is helping to reveal the cross-talk between chromatin states and nuclear organization.

View Article: PubMed Central - PubMed

Affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058, Basel, Switzerland. anna.mattout@fmi.ch.

ABSTRACT
The spatial distribution of chromatin domains in interphase nuclei changes dramatically during development in multicellular organisms. A crucial question is whether nuclear organization is a cause or a result of differentiation. Genetic perturbation of lamina-heterochromatin interactions is helping to reveal the cross-talk between chromatin states and nuclear organization.

No MeSH data available.


Related in: MedlinePlus