High Mobility Group Protein N5 (HMGN5) and Lamina-associated Polypeptide 2α (LAP2α) Interact and Reciprocally Affect Their Genome-wide Chromatin Organization

Zhang, Shaofei; Schones, Dustin E.; Malicet, Cédric; Rochman, Mark; Zhou, Ming; Foisner, Roland; Bustin, Michael

doi:10.1074/jbc.c113.469544

Cited by 23 publications

(31 citation statements)

References 27 publications

(27 reference statements)

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“…Thus, it is tempting to speculate that the dynamic pool of lamin A/C affects epigenetic pathways and chromatin accessibility, and that this role is affected by LAP2α. In line with this model, LAP2α has also been shown to influence genome-wide chromatin association of high mobility group nucleosome binding domain 5 (HMGN5), a nucleosome-binding protein involved in chromatin decompaction (Furusawa et al, 2015;Zhang et al, 2013). It remains unclear, however, whether the association to chromatin by lamin A/C or HMGN5 together with LAP2α actively generates accessible chromatin, or whether these proteins preferentially bind to "open" chromatin and keep it in an "open" state.…”

Section: Regulation Of A-type Lamins In the Nuclear Interiormentioning

confidence: 90%

“…Furthermore, overexpression of nucleosome-binding HMGN5 in cardiomyocytes has been shown to cause decompaction of chromatin as well as nuclear deformation (Furusawa et al, 2015). As LAP2α and nucleoplasmic lamin A affect the association between HMGN5 and chromatin (Zhang et al, 2013) and also chromatin mobility (Bronshtein et al, 2015), it is tempting to speculate that structures comprising A-type lamins and LAP2α contribute to the mechanical properties of the nucleus indirectly through their effect on spatial chromatin organization. In line with this hypothesis, a study that used genetically engeneered designed ankyrin-repeat proteins (DARPins) that disassemble lamins in living cells showed that these cells have a higher nuclear stiffness compared to LMNAknockout cells (Zwerger et al, 2015).…”

Section: Mechanical Functions Of Laminsmentioning

confidence: 99%

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Lamins in the nuclear interior − life outside the lamina

Naetar

Ferraioli

Foisner

2017

Journal of Cell Science

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142

136

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Nuclear lamins are components of the peripheral lamina that define the mechanical properties of nuclei and tether heterochromatin to the periphery. A-type lamins localize also to the nuclear interior, but the regulation and specific functions of this nucleoplasmic lamin pool are poorly understood. In this Commentary, we summarize known pathways that are potentially involved in the localization and dynamic behavior of intranuclear lamins, including their post-translational modifications and interactions with nucleoplasmic proteins, such as lamina-associated polypeptide 2α (LAP2α; encoded by ). In addition, new data suggest that lamins in the nuclear interior have an important role in chromatin regulation and gene expression through dynamic binding to both hetero- and euchromatic genomic regions and promoter subdomains, thereby affecting epigenetic pathways and chromatin accessibility. Nucleoplasmic lamins also have a role in spatial chromatin organization and may be involved in mechanosignaling. In view of this newly emerging concept, we propose that the previously reported cellular phenotypes in lamin-linked diseases are, at least in part, rooted in an impaired regulation and/or function of the nucleoplasmic lamin A/C pool.

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Section: Regulation Of A-type Lamins In the Nuclear Interiormentioning

confidence: 90%

Section: Mechanical Functions Of Laminsmentioning

confidence: 99%

Lamins in the nuclear interior − life outside the lamina

Naetar

Ferraioli

Foisner

2017

Journal of Cell Science

Self Cite

142

136

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“…Although it is currently difficult to demonstrate, the concept of 'internal LADs' has been proposed 5,12 based on fluorescence tagging of lamin-interacting sequences by DamID, 5 fluorescence in situ hybridization of LMNA-associated loci, 12,33 and the existence of a nucleoplasmic pool of LMNA 27,28,32 which may interact with chromatin. Interaction of the lamina-associated polypeptide LAP2a with intranuclear A-type lamins 27 and association of LAP2a with chromosomes 34,35 strongly argue in favor of an intranuclear pool of LMNA directly or indirectly interacting with chromatin.…”

Section: Discussionmentioning

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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“…2) including histone methyltransferases such as Suv39H1, histones such as H2, H3, and H4, 34 the heterochromatin proteins HP1alpha 31 and β, bridging proteins such as LAP2alpha and BAF, which in turn bind nucleosomal proteins. The lamin A/C and prelamin A binding partner LAP2alpha associates with the nucleosomal protein HMGN5 within a protein platform that should regulate chromatin mobility and the degree of heterochromatin condensation 32 , 33 . HP1 interaction with lamins is required for heterochromatin anchorage at the end of mitosis, 31 another key role of lamins in chromatin dynamics.…”

Section: Why Chromatin Needs Laminsmentioning

confidence: 99%

Diverse lamin-dependent mechanisms interact to control chromatin dynamics

Camozzi

Capanni

Cenni

et al. 2014

Nucleus

113

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Interconnected functional strategies govern chromatin dynamics in eukaryotic cells. In this context, A and B type lamins, the nuclear intermediate filaments, act on diverse platforms involved in tissue homeostasis. On the nuclear side, lamins elicit large scale or fine chromatin conformational changes, affect DNA damage response factors and transcription factor shuttling. On the cytoplasmic side, bridging-molecules, the LINC complex, associate with lamins to coordinate chromatin dynamics with cytoskeleton and extra-cellular signals. Consistent with such a fine tuning, lamin mutations and/or defects in their expression or post-translational processing, as well as mutations in lamin partner genes, cause a heterogeneous group of diseases known as laminopathies. They include muscular dystrophies, cardiomyopathy, lipodystrophies, neuropathies, and progeroid syndromes. The study of chromatin dynamics under pathological conditions, which is summarized in this review, is shedding light on the complex and fascinating role of the nuclear lamina in chromatin regulation.

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High Mobility Group Protein N5 (HMGN5) and Lamina-associated Polypeptide 2α (LAP2α) Interact and Reciprocally Affect Their Genome-wide Chromatin Organization

Cited by 23 publications

References 27 publications

Lamins in the nuclear interior − life outside the lamina

Lamins in the nuclear interior − life outside the lamina

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

Diverse lamin-dependent mechanisms interact to control chromatin dynamics

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