The repressive genome compartment is established early in the cell cycle before forming the lamina associated domains

Luperchio, Teresa Romeo; Sauria, Michael E.G.; Hoskins, Victoria E.; Wong, Xianrong; DeBoy, Emily A.; Gaillard, Marie Cécile; Tsang, Peter; Pekrun, Katja; Ach, Robert A.; Yamada, N. Alice; Taylor, James; Reddy, Karen L.

doi:10.1101/481598

Cited by 23 publications

(71 citation statements)

References 69 publications

(117 reference statements)

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“…These data suggest, and support previous findings, that these regions are enriched for chromatin complexes that initiate and maintain a heterochromatic state [10,12] . These data also support a model in which chromatin state is established independently from association of these chromatin domains with the lamina, since these proteins do not interact with the INM/lamin directly [15,17] .…”

Section: Integration Of Laminome and Ladome Data Identify Unique And supporting

confidence: 79%

“…The LAD-specific proteins include the previously described chromatin modifier complexes such as EHMT1/2, cell cycle regulators and chromatin interactors. This is particularly interesting given the recent evidence that chromatin state directs LAD organization [12,[14][15][16][17][18] . These data suggest, and support previous findings, that these regions are enriched for chromatin complexes that initiate and maintain a heterochromatic state [10,12] .…”

Section: Integration Of Laminome and Ladome Data Identify Unique And mentioning

confidence: 98%

“…Moreover, recent studies have highlighted that both H3K9me2/3 and H3K27me3 are involved in LAD organization [12][13][14][15][16] . LADs represent a large fraction of the genome (30-50%, depending upon the cell type) and are highly correlated with the so-called heterochromatic "B-compartment", as identified by chromatin conformation capture assays (HiC) [13,17,18] . Given their importance to cellular function and identity, it is important to understand how these large domains of heterochromatin are regulated, maintained, and formed in order to understand global genome regulation and organization.…”

Section: Introductionmentioning

confidence: 99%

“…In addition to H3K27me3 and H3K9me2/3, A-type lamins and the inner nuclear membrane (INM) proteins lamina-associated polypeptide beta (LAP2β) and Lamin B Receptor (LBR) have been implicated in organizing LADs [12,[17][18][19][20] . The nuclear lamina is a proteinaceous network of type V intermediate filaments comprising A and B type lamins.…”

Section: Introductionmentioning

confidence: 99%

“…The nuclear lamina is a proteinaceous network of type V intermediate filaments comprising A and B type lamins. These coiled-coil domain proteins provide a structural scaffold at the INM, with the A-type lamins being shown to mediate LAD organization [12,[17][18][19] . Longstanding efforts have been undertaken to map and characterize the local proteome of the nuclear lamina of the INM using inner nuclear membrane preparations, co-immunoprecipitation and, more recently, BioID ( Bio tinylation Id entification), a method for detecting proximal protein interactions in living cells [21][22][23][24][25] .…”

Section: Introductionmentioning

confidence: 99%

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Mapping the micro-proteome of the nuclear lamina and lamin associated domains

Cutler

Wong

Hoskins

et al. 2019

Preprint

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The nuclear lamina is a proteinaceous network of filaments that provide both structural and gene regulatory functions by tethering proteins and large domains of DNA, so-called lamin associated domains (LADs), to the periphery of the nucleus. LADs are a large fraction of the mammalian genome that are repressed, in part, by their association to the nuclear periphery. The genesis and maintenance of LADs is poorly understood as are the proteins that participate in these functions.In an effort to identify proteins that reside at the nuclear periphery and potentially interact with LADs, we have taken a two-pronged approach. First, we have undertaken an interactome analysis of the inner nuclear membrane bound LAP2β to further characterize the nuclear lamina proteome. To accomplish this, we have leveraged the BioID system, which previously has been successfully used to characterize the nuclear lamina proteome. Second, we have established a system to identify proteins that bind to LADs by developing a chromatin directed BioID system. We combined the BioID system with the m6A-tracer system which binds to LADs in live cells to identify both LAD proximal and nuclear lamina proteins. In combining these datasets, we have further characterized the protein network at the nuclear lamina, identified putative LAD proximal proteins and found several proteins that appear to interface with both micro-proteomes. Importantly, several proteins essential for LAD function, including heterochromatin regulating proteins related to H3K9 methylation, were identified in this study.

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Section: Integration Of Laminome and Ladome Data Identify Unique And supporting

confidence: 79%

Section: Integration Of Laminome and Ladome Data Identify Unique And mentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Mapping the micro-proteome of the nuclear lamina and lamin associated domains

Cutler

Wong

Hoskins

et al. 2019

Preprint

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Choreography of lamina‐associated domains: structure meets dynamics

Alagna,

Thomas,

Wilson

et al. 2023

FEBS Letters

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Lamina‐associated domains are large regions of heterochromatin positioned at the nuclear periphery. These domains have been implicated in gene repression, especially in the context of development. In mammals, LAD organization is dependent on nuclear lamins, inner nuclear membrane proteins, and chromatin state. In addition, chromatin readers and modifier proteins have been implicated in this organization, potentially serving as molecular tethers that interact with both nuclear envelope proteins and chromatin. More recent studies have focused on teasing apart the rules that govern dynamic LAD organization and how LAD organization, in turn, relates to gene regulation and overall 3D genome organization. This review highlights recent studies in mammalian cells uncovering factors that instruct the choreography of LAD organization, re‐organization, and dynamics at the nuclear lamina, including LAD dynamics in interphase and through mitotic exit, when LAD organization is re‐established, as well as intra‐LAD subdomain variations.

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Two major mechanisms of chromosome organization

Mirny

Imakaev

Abdennur

2019

Current Opinion in Cell Biology

179

174

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The spatial organization of chromosomes has long been connected to their polymeric nature (e.g. [1]) and is believed to be important for their biological functions, including the control of interactions between genomic elements, the maintenance of genetic information, and the compaction and safe transfer of chromosomes to cellular progeny. Chromosome Conformation Capture techniques, particularly Hi-C, have provided a comprehensive picture of spatial chromosome organization and revealed new features and elements of chromosome folding. Furthermore, recent advances in microscopy have made it possible to obtain distance maps for extensive regions of chromosomes ([2] [3]), providing information complementary to, and in excellent agreement with, Hi-C maps. Not only has the resolution of both techniques advanced significantly, but new perturbation data generated in the last two years have led to the identification of molecular mechanisms behind large-scale genome organization. Two major mechanisms that have been proposed to govern chromosome organization are (i) the active (ATPdependent) process of loop extrusion by Structural Maintenance of Chromosomes (SMC) complexes, and (ii) the spatial compartmentalization of the genome, which is likely mediated by affinity interactions rather than by ATP-dependent processes. Here we review existing evidence that these two processes operate together to fold chromosomes in interphase and that loop extrusion alone drives mitotic compaction. We discuss possible implications of these mechanisms for chromosome function. "A map is not the territory it represents, but, if correct, it has a similar structure to the territory, which accounts for its usefulness." -Alfred Korzybski [4].

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The repressive genome compartment is established early in the cell cycle before forming the lamina associated domains

Cited by 23 publications

References 69 publications

Mapping the micro-proteome of the nuclear lamina and lamin associated domains

Mapping the micro-proteome of the nuclear lamina and lamin associated domains

Choreography of lamina‐associated domains: structure meets dynamics

Two major mechanisms of chromosome organization

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