LBR and Lamin A/C Sequentially Tether Peripheral Heterochromatin and Inversely Regulate Differentiation

Solovei, Irina; Wang, Audrey S.; Thanisch, Katharina; Schmidt, Christine S.; Krebs, Stefan; Zwerger, Monika; Cohen, Tatiana V.; Devys, Didier; Foisner, Roland; Peichl, Leo; Herrmann, Harald; Blum, Helmut; Engelkamp, Dieter; Stewart, Colin L.; Leonhardt, Heinrich; Joffe, Boris

doi:10.1016/j.cell.2013.01.009

Cited by 712 publications

(899 citation statements)

References 57 publications

Supporting

Mentioning

804

Contrasting

Unclassified

Order By: Relevance

“…Our studies indicate that OSNs lack not only LBR, but also lamin A, which is thought to be important for the maintenance of a peripheral heterochromatin compartment in the absence of LBR (35). However, we find that OSNs do express LAP2β, another lamina-associated protein that may tether heterochromatin, and Taar genes, to the nuclear periphery.…”

Section: Discussioncontrasting

confidence: 45%

“…Thus, OSNs lack not only LBR, but also lamin A. Previous studies have shown that the loss of both LBR and lamin A can cause an inverted nuclear architecture in cell types with a conventional nuclear architecture, resulting in the appearance of a large central heterochromatin aggregate (35). It is conceivable that the related nuclear architecture of OSNs similarly derives from the lack of both proteins.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Olfactory receptor genes expressed in distinct lineages are sequestered in different nuclear compartments

Yoon

Ragoczy

et al. 2015

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

View full text Add to dashboard Cite

The olfactory system translates a vast array of volatile chemicals into diverse odor perceptions and innate behaviors. Odor detection in the mouse nose is mediated by 1,000 different odorant receptors (ORs) and 14 trace amine-associated receptors (TAARs). ORs are used in a combinatorial manner to encode the unique identities of myriad odorants. However, some TAARs appear to be linked to innate responses, raising questions about regulatory mechanisms that might segregate OR and TAAR expression in appropriate subsets of olfactory sensory neurons (OSNs). Here, we report that OSNs that express TAARs comprise at least two subsets that are biased to express TAARs rather than ORs. The two subsets are further biased in Taar gene choice and their distribution within the sensory epithelium, with each subset preferentially expressing a subgroup of Taar genes within a particular spatial domain in the epithelium. Our studies reveal one mechanism that may regulate the segregation of Olfr (OR) and Taar expression in different OSNs: the sequestration of Olfr and Taar genes in different nuclear compartments. Although most Olfr genes colocalize near large central heterochromatin aggregates in the OSN nucleus, Taar genes are located primarily at the nuclear periphery, coincident with a thin rim of heterochromatin. Taar-expressing OSNs show a shift of one Taar allele away from the nuclear periphery. Furthermore, examination of hemizygous mice with a single Taar allele suggests that the activation of a Taar gene is accompanied by an escape from the peripheral repressive heterochromatin environment to a more permissive interior chromatin environment. olfactory receptor genes | Taar genes | nuclear organization

show abstract

Section: Discussioncontrasting

confidence: 45%

Section: Resultsmentioning

confidence: 99%

Olfactory receptor genes expressed in distinct lineages are sequestered in different nuclear compartments

Yoon

Ragoczy

et al. 2015

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

View full text Add to dashboard Cite

show abstract

“…Consistent with this, dissociation from the lamina in Lamin A-mutant human cell lines did not necessarily lead to gene activation (Kubben et al 2012). Moreover, mutations in the lamin B receptor and lamin A genes led to a loss of peripheral heterochromatin in post-mitotic mouse cells (Solovei et al 2013). In these cells, where heterochromatin centers around pericentromeric satellite repeats in the nuclear interior, no large-scale transcriptional changes were detected (Solovei et al 2013).…”

Section: Potential Functional Contribution Of Pericentromere Associationmentioning

confidence: 55%

“…Moreover, mutations in the lamin B receptor and lamin A genes led to a loss of peripheral heterochromatin in post-mitotic mouse cells (Solovei et al 2013). In these cells, where heterochromatin centers around pericentromeric satellite repeats in the nuclear interior, no large-scale transcriptional changes were detected (Solovei et al 2013). Thus, gene repression and the spatial segregation of active and inactive chromatin can be maintained in a radial position-independent manner.…”

Section: Potential Functional Contribution Of Pericentromere Associationmentioning

confidence: 99%

Characterization and dynamics of pericentromere-associated domains in mice

et al. 2015

View full text Add to dashboard Cite

Despite recent progress in genome topology knowledge, the role of repeats, which make up the majority of mammalian genomes, remains elusive. Satellite repeats are highly abundant sequences that cluster around centromeres, attract pericentromeric heterochromatin, and aggregate into nuclear chromocenters. These nuclear landmark structures are assumed to form a repressive compartment in the nucleus to which genes are recruited for silencing. We have designed a strategy for genome-wide identification of pericentromere-associated domains (PADs) in different mouse cell types. The ∼1000 PADs and non-PADs have similar chromatin states in embryonic stem cells, but during lineage commitment, chromocenters progressively associate with constitutively inactive genomic regions at the nuclear periphery. This suggests that PADs are not actively recruited to chromocenters, but that chromocenters are themselves attracted to inactive chromatin compartments. However, we also found that experimentally induced proximity of an active locus to chromocenters was sufficient to cause gene repression. Collectively, our data suggest that rather than driving nuclear organization, pericentromeric satellite repeats mostly co-segregate with inactive genomic regions into nuclear compartments where they can contribute to stable maintenance of the repressed status of proximal chromosomal regions.[Supplemental material is available for this article.]One of the major challenges in genome biology is to understand how the genome is organized and what factors control the spatiotemporal expression patterns of genes in different cell types. It is well established that higher-order organization of chromatin within the three-dimensional space of the nucleus is an important contributor to regulation of gene expression. In particular, long-range physical interactions of genomic elements in the nuclear space enable functional communication between genes and their regulatory DNA elements that can be hundreds of kilobases apart on the linear

show abstract

“…By contrast, diurnal mammals have conventionally organized rod cell nuclei. Now Solovei et al 4 have followed up on these studies by demonstrating that this insideout architecture they discovered is due to a hitherto unknown and unanticipated absence of both lamin A/C and LBR in rod nuclei of adult nocturnal mammals (Fig. 1A, top row).…”

mentioning

confidence: 99%