Lamina-associated polypeptide (LAP)2α and nucleoplasmic lamins in adult stem cell regulation and disease

Gesson, Kevin; Vidak, Sandra; Foisner, Roland

doi:10.1016/j.semcdb.2013.12.009

Cited by 73 publications

(78 citation statements)

References 137 publications

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“…However, post-differentiation LADs contain repressive chromatin features and strongly coincidewith GADs. As lamin A/C is found both at the nuclear periphery and in the nuclear interior (Dechat et al 2010;Gesson et al 2014), the heterochromatic versus euchromatic nature of lamin A/C-chromatin interactions evidenced in this study is likely influenced by the dual localization of A-type lamins: Peripheral LADs are enriched in heterochromatin (Guelen et al 2008;Reddy et al 2008), while nucleoplasmic LADs would be more euchromatic. Extending the dogma that LADs are mainly gene poor and transcriptionally inactive, our results indicate that lamin A/C LADs can be found both in active and repressive chromatin contexts, which can be influenced by cell differentiation status.…”

Section: Discussionmentioning

confidence: 73%

“…Cold Spring Harbor Laboratory Press on May 11, 2018 -Published by genome.cshlp.org Downloaded from periphery (Gesson et al 2014), a process regulated by LAP2 (Naetar et al 2008), and this could potentially generate new LADs. Interestingly, LAP2 also modulates the balance between tissue progenitor cell proliferation and differentiation (Dorner et al 2006;Naetar and Foisner 2009;.…”

Section: Wwwgenomeorgmentioning

confidence: 99%

“…Interestingly, LAP2 overexpression in mouse preadipocytes elicits adipogenic differentiation (Dorner et al 2006), suggesting that maintenance of an intranuclear lamin A/C pool is important for adipogenesis. Nucleoplasmic lamin A/C appears therefore to be critical for differentiation of tissue progenitor cells and may play important roles regulating chromatin and gene expression in the nuclear interior (Dechat et al 2010;Gesson et al 2014).…”

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confidence: 99%

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Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B

et al. 2015

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Dynamic interactions of nuclear lamins with chromatin through lamin-associated domains (LADs) contribute to spatial arrangement of the genome. Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C–chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. Lamin A/C LADs are found both in active and repressive chromatin contexts that can be influenced by cell differentiation status. De novo formation of adipogenic lamin A/C LADs occurs nonrandomly on GADs, which consist of megabase-size intergenic and repressive chromatin domains. Accordingly, whereas predifferentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. Release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional up-regulation after adipogenic induction, and with downstream elevations in H2BS112GlcNAc levels and O-GlcNAc cycling. Our results unveil an epigenetic prepatterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification.

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Section: Discussionmentioning

confidence: 73%

Section: Wwwgenomeorgmentioning

confidence: 99%

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confidence: 99%

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Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B

et al. 2015

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“…LAP2alpha has several means to interact with chromatin and DNA, including a LEM and LEM-like motif (Gesson et al 2014), and was recently reported to associate with chromatin in vivo on a genome-wide level .…”

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confidence: 99%

A-type lamins bind both hetero- and euchromatin, the latter being regulated by lamina-associated polypeptide 2 alpha

et al. 2016

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Lamins are components of the peripheral nuclear lamina and interact with heterochromatic genomic regions, termed lamina-associated domains (LADs). In contrast to lamin B1 being primarily present at the nuclear periphery, lamin A/C also localizes throughout the nucleus, where it associates with the chromatin-binding protein lamina-associated polypeptide (LAP) 2 alpha. Here, we show that lamin A/C also interacts with euchromatin, as determined by chromatin immunoprecipitation of euchromatin-and heterochromatin-enriched samples. By way of contrast, lamin B1 was only found associated with heterochromatin. Euchromatic regions occupied by lamin A/C overlap with those bound by LAP2alpha, and lack of LAP2alpha in LAP2alpha-deficient cells shifts binding of lamin A/C toward more heterochromatic regions. These alterations in lamin A/C-chromatin interactions correlate with changes in epigenetic histone marks in euchromatin but do not significantly affect gene expression. Loss of lamin A/C in heterochromatic regions in LAP2alpha-deficient cells, however, correlated with increased gene expression. Our data show a novel role of nucleoplasmic lamin A/C and LAP2alpha in regulating euchromatin.

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“…LAP2α forms a stable complex with lamin-A/C in the nucleoplasm in interphase cells in order to maintain the cell in a proliferative state by controlling localization and phosphorylation of the retinoblastoma-associated protein (Rb) (Dechat et al, 2000;Pekovic et al, 2007). LAP2α can also regulate the nucleoplasmic lamin-A/C pool, but the mechanisms remains elusive (Gesson et al, 2014). BAF1 is an evolutionarily conserved small protein that binds to chromatin DNA and histones.…”

Section: Introductionmentioning

confidence: 99%

Lamin-A/C/LAP2α/BAF1 protein complex regulates the mitotic spindle assembly and positioning

Wang

et al. 2015

Journal of Cell Science

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Some nuclear proteins that are crucial in interphase relocate during the G2/M-phase transition in order to perform their mitotic functions. However, how they perform these functions and the underlying mechanisms remain largely unknown. Here, we report that a fraction of the nuclear periphery proteins lamin-A/C, LAP2α and BAF1 (also known as BANF1) relocate to the spindle and the cell cortex in mitosis. Knockdown of these proteins by using RNA interference (RNAi) induces short and fluffy spindle formation, and disconnection of the spindle from the cell cortex. Disrupting the microtubule assembly leads to accumulation of these proteins in the cell cortex, whereas depolymerizing the actin microfilaments results in the formation of short spindles. We further demonstrate that these proteins are part of a stable complex that links the mitotic spindle to the cell cortex and the spindle matrix by binding to spindle-associated dynein, the actin filaments in the cell cortex and the spindle matrix. Taken together, our findings unveil a unique mechanism where the nuclear periphery proteins lamin-A/C, LAP2α and BAF1 are assembled into a protein complex during mitosis in order to regulate assembly and positioning of the mitotic spindle.

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Lamina-associated polypeptide (LAP)2α and nucleoplasmic lamins in adult stem cell regulation and disease

Cited by 73 publications

References 137 publications

Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B

Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B

A-type lamins bind both hetero- and euchromatin, the latter being regulated by lamina-associated polypeptide 2 alpha

Lamin-A/C/LAP2α/BAF1 protein complex regulates the mitotic spindle assembly and positioning

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