Nuclear neighborhoods and gene expression

Current Opinion in Genetics and Development

Volumn 19, Issue 2, 2009, Pages 172-179

  Zhao, Rui ^a   Bodnar, Megan S ^b   Spector, David L ^a,b  

^a STONY BROOK UNIVERSITY   (United States)

^b Howard Hughes Medical Institute Cold Spring Harbor Laboratory Cold Spring Harbor   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL NUCLEUS INCLUSION BODY; CELL NUCLEUS MEMBRANE; DNA REPLICATION; DNA SEQUENCE; GENE EXPRESSION; GENE REPRESSION; GENOME ANALYSIS; HUMAN; NONHUMAN; NUCLEAR LAMINA; NUCLEAR PORE COMPLEX; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW;

ANIMALS; CELL NUCLEOLUS; CELL NUCLEUS; CHROMATIN; COILED BODIES; GENE EXPRESSION REGULATION; HETEROCHROMATIN; HUMANS; MODELS, BIOLOGICAL; NUCLEAR ENVELOPE;

EUKARYOTA;

EID: 65349090225     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.gde.2009.02.007     Document Type: Review

References (53)

1. Fraser P., and Bickmore W. Nuclear organization of the genome and the potential for gene regulation. Nature 447 (2007) 413-417
2. Kumaran R.I., Thakar R., and Spector D.L. Chromatin dynamics and gene positioning. Cell 132 (2008) 929-934
3. Cremer T., Cremer M., Dietzel S., Müller S., Solovei I., and Fakan S. Chromosome territories - a functional nuclear landscape. Curr Opin Cell Biol 18 (2006) 307-316
4. Spector D.L. SnapShot: cellular bodies. Cell 127 (2006) 1071
5. Takizawa T., Meaburn K.J., and Misteli T. The meaning of gene positioning. Cell 135 (2008) 9-13
6. Küpper K., Kölbl A., Biener D., Dittrich S., von Hase J., Thormeyer T., Fiegler H., Carter N.P., Speicher M.R., Cremer T., et al. Radial chromatin positioning is shaped by local gene density, not by gene expression. Chromosoma 116 (2007) 285-306
7. Lanctôt C., Kaspar C., and Cremer T. Positioning of the mouse Hox gene clusters in the nuclei of developing embryos and differentiating embryoid bodies. Exp Cell Res 313 (2007) 1449-1459
8. Meaburn K.J., and Misteli T. Locus-specific and activity-independent gene repositioning during early tumorigenesis. J Cell Biol 180 (2008) 39-50. A number of nonrandom gene repositioning events were identified during differentiation in a 3D mammary epithelial cell culture model, and during tumorigenesis, the alterations of spatial positioning patterns were found to be unrelated to gene activity. This study presents an example of activity-independent genome repositioning events that occur in the early stages of tumor formation.
9. Augui S., Filion G.J., Huart S., Nora E., Guggiari M., Maresca M., Stewart A.F., and Heard E. Sensing X chromosome pairs before X inactivation via a novel X-pairing region of the Xic. Science 318 (2007) 1632-1636. This study utilizes 3D RNA and DNA FISH to identify a novel X-pairing region (Xpr) of the X inactivation center (Xic) that drives Xic trans-associations. Importantly, the authors propose that the Xpr may coordinate reciprocal Xist/Tsix expression during X chromosome inactivation.
10. Bacher C.P., Guggiari M., Brors B., Augui S., Clerc P., Avner P., Eils R., and Heard E. Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation. Nat Cell Biol 8 (2006) 293-299
11. Kosak S.T., Scalzo D., Alworth S.V., Li F., Palmer S., Enver T., Lee J.S., and Groudine M. Coordinate gene regulation during hematopoiesis is related to genomic organization. PLoS Biol 5 (2007) e309
12. Noordermeer D., Branco M.R., Splinter E., Klous P., van Ijcken W., Swagemakers S., Koutsourakis M., van der Spek P., Pombo A., and De Laat W. Transcription and chromatin organization of a housekeeping gene cluster containing an integrated beta-globin locus control region. PLoS Genet 4 (2008) e1000016. The human beta-globin locus control region (LCR) was targeted in two opposite orientations to a gene-dense region in the mouse genome containing mostly housekeeping genes. Analysis of the dynamics of the integrated LCR revealed that although it was able to influence the expression of surrounding genes, transcriptional enhancement was not due to repositioning of the locus outside its chromosome territory (CT), as previously reported. Rather, the authors conclude that LCR makes gene contacts via chromatin looping, leading to enhanced transcription of LCR-associated genes.
13. Osborne C.S., Chakalova L., Mitchell J.A., Horton A., Wood A.L., Bolland D.J., Corcoran A.E., and Fraser P. Myc dynamically and preferentially relocates to a transcription factory occupied by Igh. PLoS Biol 5 (2007) e192
14. Xu M., and Cook P.R. The role of specialized transcription factories in chromosome pairing. Biochim Biophys Acta 1783 (2008) 2155-2160
15. Xu N., Tsai C.L., and Lee J.T. Transient homologous chromosome pairing marks the onset of X inactivation. Science 311 (2006) 1149-1152
16. Brown J.M., Green J., das Neves R.P., Wallace H.A., Smith A.J., Hughes J., Gray N., Taylor S., Wood W.G., Higgs D.R., et al. Association between active genes occurs at nuclear speckles and is modulated by chromatin environment. J Cell Biol 182 (2008) 1083-1097. Using human erythropoiesis as a model, the authors report that five cotranscribed genes spatially associate with each other in the nucleus at significant but variable frequencies. Interestingly, the cotranscribed genes were found to cluster around nuclear speckles, contradicting earlier studies that implicate transcription foci in the clustering of cotranscribed genes. This study suggests that nuclear speckles form de novo after cell division by the recruitment of splicing factors to active genes, and subsequent association of genes at a common nuclear speckle is facilitated by chromatin dynamics.
17. Finlan L.E., Sproul D., Thomson I., Boyle S., Kerr E., Perry P., Ylstra B., Chubb J.R., and Bickmore W.A. Recruitment to the nuclear periphery can alter expression of genes in human cells. PLoS Genet 4 (2008) e1000039. Relocation of specific human chromosomes to the nuclear periphery by tethering them to an inner nuclear membrane protein Lap2-beta can reversibly suppress the expression of some endogenous human genes, meanwhile the expression of many other genes is not detectably reduced.
18. Grund S.E., Fischer T., Cabal G.G., Antúnez O., Pérez-Ortín J.E., and Hurt E. The inner nuclear membrane protein Src1 associates with subtelomeric genes and alters their regulated gene expression. J Cell Biol 182 (2008) 897-910. This study reveals that the integral inner nuclear membrane protein Src1 is associated with subtelomeric chromatin. This may either help cluster genes for cooperative gene regulation at the nuclear periphery or facilitate the TREX-dependent messenger RNA export though the nuclear pore complexes. Src1 provides a good example for understanding the complex role of inner nuclear membrane proteins in gene expression.
19. Hu Q., Kwon Y.S., Nunez E., Cardamone M.D., Hutt K.R., Ohgi K.A., Garcia-Bassets I., Rose D.W., Glass C.K., Rosenfeld M.G., et al. Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules. Proc Natl Acad Sci U S A 105 (2008) 19199-19204. The authors report rapid, dynamic, hormone-induced, and actin-dependent reorganization of estrogen receptor alpha (ERα) responsive genes close to nuclear speckles. Repositioning of genes to nuclear speckles was associated with enhanced transcription. Evidence is presented that suggests nuclear speckles could act as 'hubs' of inter-chromosomal interactions.
20. Kumar P.P., Bischof O., Purbey P.K., Notani D., Urlaub H., Dejean A., and Galande S. Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus. Nat Cell Biol 9 (2007) 45-56
21. Kumaran R.I., and Spector D.L. A genetic locus targeted to the nuclear periphery in living cells maintains its transcriptional competence. J Cell Biol 180 (2008) 51-65. Repositioning an inducible gene locus to the nuclear lamina by LacI-LaminB1 was not sufficient to inhibit inducible gene activation. Interestingly, repositioning required passage through mitosis. Components of the gene expression machinery are recruited to the targeted locus with kinetics similar to the nontargeted locus. This 200-copy transgene array driven by a strong activator may create a microenvironment to counteract the repressive effects of the nuclear periphery or it may have incorporated into an existing microenvironment that is permissive to transcriptional activation.
22. Mohammad F., Pandey R.R., Nagano T., Chakalova L., Mondal T., Fraser P., and Kanduri C. Kcnq1ot1/Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region. Mol Cell Biol 28 (2008) 3713-3728. Using an episomal vector system, this study characterizes a silencing domain (SD) at the 5′-end of the Kcnq1ot1 antisense noncoding RNA (ncRNA), an ncRNA that has been implicated in transcriptional silencing of linked genes. The SD region of the Kcnqlot1 transcript was found to be necessary for the bidirectional spread of H3K9 trimethylation to neighboring chromosomal regions. Intriguingly, the authors also find that the SD domain is also required to target the episomal vector to the perinucleolar chromatin compartment. Collectively, these data suggest a model where an antisense ncRNA mediates transcriptional gene silencing by targeting genes to a heterochromatic nuclear compartment.
23. Reddy K.L., Zullo J.M., Bertolino E., and Singh H. Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature 452 (2008) 243-247. Repositioning of a specific genetic locus to the inner nuclear membrane (INM) using an LacI-emerin fusion protein resulted in transcriptional repression of many genes on the associated chromosome. Interestingly, repositioning of the gene locus required passage through mitosis.
24. Taddei A., Van Houwe G., Hediger F., Kalck V., Cubizolles F., Schober H., and Gasser S.M. Nuclear pore association confers optimal expression levels for an inducible yeast gene. Nature 441 (2006) 774-778. The authors report that a subtelomeric gene, hexokinase isoenzyme 1 (HXK1), associated with nuclear pores through its 3′-untranslated region (UTR) in a transcription-dependent manner. This finding suggests that nuclear position is actively involved in optimizing gene expression levels.
25. Takizawa T., Gudla P.R., Guo L., Lockett S., and Misteli T. Allele-specific nuclear positioning of the monoallelically expressed astrocyte marker GFAP. Genes Dev 22 (2008) 489-498. This study examines the nuclear positioning of the mono-allelically expressed astrocyte-specific glial fibrillary acidic protein (GFAP) gene. The authors note that GFAP alleles are differentially positioned within the nucleus, and that an allele's radial position is dependent on gene activity. Interestingly, this report also provides evidence that the active allele of GFAP frequently associates with nuclear speckles.
26. Zhang L.F., Huynh K.D., and Lee J.T. Perinucleolar targeting of the inactive X during S phase: evidence for a role in the maintenance of silencing. Cell 129 (2007) 693-706. This study addresses the question of how mammalian female cells maintain silencing of the inactive X chromosome (Xi) over successive cell division cycles. The authors present evidence that the Xi associates with perinucleolar heterochromatin, while the active X chromosome does not. Curiously, the Xi-perinucleolar associations occurred largely during mid-to-late S-phase. Thus, these data suggest a role for the perinucleolar heterochromatic region in the maintenance of Xi silencing during S-phase.
27. Lanctôt C., Cheutin T., Cremer M., Cavalli G., and Cremer T. Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nat Rev Genet 8 (2007) 104-115
28. Chuang C.H., and Belmont A.S. Moving chromatin within the interphase nucleus-controlled transitions?. Semin Cell Dev Biol 18 (2007) 698-706
29. Fawcett D.W. Nucleus. In The Cell. edn 2nd (1981), W.B. Saunders Company 195-302
30. Dechat T., Pfleghaar K., Sengupta K., Shimi T., Shumaker D.K., Solimando L., and Goldman R.D. Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev 22 (2008) 832-853
31. Heessen S., and Fornerod M. The inner nuclear envelope as a transcription factor resting place. EMBO Rep 8 (2007) 914-919
32. Mattout A., Goldberg M., Tzur Y., Margalit A., and Gruenbaum Y. Specific and conserved sequences in D. melanogaster and C. elegans lamins and histone H2A mediate the attachment of lamins to chromosomes. J Cell Sci 120 (2007) 77-85
33. Pickersgill H., Kalverda B., De Wit E., Talhout W., Fornerod M., and van Steensel B. Characterization of the Drosophila melanogaster genome at the nuclear lamina. Nat Genet 38 (2006) 1005-1014. Using the DamID method, the authors identified ∼500 Drosophila melanogaster genes that interact with B-type lamin (Lam), all of which exhibited repressed gene expression. This Lam-association can be interrupted by enhanced acetylation. This study shows that the nuclear lamina can function in both chromatin positioning and gene regulation.
34. Guelen L., Pagie L., Brasset E., Meuleman W., Faza M.B., Talhout W., Eussen B.H., de Klein A., Wessels L., De Laat W., et al. Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453 (2008) 948-951. In this study, the authors generate a high-resolution DamID map of nuclear lamina (NL) interactions in human lung fibroblasts. The map shows more than 1300 sharply defined large, discrete lamina-associated domains (LADs) characterized by low gene expression levels. This result suggests the NL not only serves as a transcriptionally inactive region but also plays an important role in genome organization.
35. Mekhail K., Seebacher J., Gygi S.P., and Moazed D. Role for perinuclear chromosome tethering in maintenance of genome stability. Nature 456 (2008) 667-670
36. King M.C., Drivas T.G., and Blobel G. A network of nuclear envelope membrane proteins linking centromeres to microtubules. Cell 134 (2008) 427-438
37. Somech R., Shaklai S., Geller O., Amariglio N., Simon A.J., Rechavi G., and Gal-Yam E.N. The nuclear-envelope protein and transcriptional repressor LAP2beta interacts with HDAC3 at the nuclear periphery, and induces histone H4 deacetylation. J Cell Sci 118 (2005) 4017-4025
38. Tang C.W., Maya-Mendoza A., Martin C., Zeng K., Chen S., Feret D., Wilson S.A., and Jackson D.A. The integrity of a lamin-B1-dependent nucleoskeleton is a fundamental determinant of RNA synthesis in human cells. J Cell Sci 121 (2008) 1014-1024
39. Tran E.J., and Wente S.R. Dynamic nuclear pore complexes: life on the edge. Cell 125 (2006) 1041-1053
40. Schmid M., Arib G., Laemmli C., Nishikawa J., Durussel T., and Laemmli U.K. Nup-PI: the nucleopore-promoter interaction of genes in yeast. Mol Cell 21 (2006) 379-391
41. Rougemaille M., Dieppois G., Kisseleva-Romanova E., Gudipati R.K., Lemoine S., Blugeon C., Boulay J., Jensen T.H., Stutz F., Devaux F., et al. THO/Sub2p functions to coordinate 3′-end processing with gene-nuclear pore association. Cell 135 (2008) 308-321. A mutation in THO/sub2p was shown to result in the accumulation of a stalled intermediate in mRNP synthesis, which contained nuclear pore components and polyadenylation factors associated with chromatin. These findings suggest that the THO/sub2p complex functions after the commitment to 3′-end processing, and plays a role in coordinating mRNP export.
42. Brown C.R., and Silver P.A. Transcriptional regulation at the nuclear pore complex. Curr Opin Genet Dev 17 (2007) 100-106
43. Luthra R., Kerr S.C., Harreman M.T., Apponi L., Fasken H., Ramineni M.B., Chaurasia S.S., Valentini S.R., and Corbett A.H. Actively transcribed GAL genes can be physically linked to the nuclear pore by the SAGA chromatin modifying complex. J Biol Chem 282 (2007) 3042-3049
44. Ryan C.M., Harries J.C., Kindle K.B., Collins H.M., and Heery D.M. Functional interaction of CREB binding protein (CBP) with nuclear transport proteins and modulation by HDAC inhibitors. Cell Cycle 5 (2006) 2146-2152
45. Brown C.R., Kennedy C.J., Delmar V.A., Forbes D.J., and Silver P.A. Global histone acetylation induces functional genomic reorganization at mammalian nuclear pore complexes. Genes Dev 22 (2008) 627-639
46. Brickner D.G., Cajigas I., Fondufe-Mittendorf Y., Ahmed S., Lee P.C., Widom J., and Brickner J.H. H2A. Z-mediated localization of genes at the nuclear periphery confers epigenetic memory of previous transcriptional state. PLoS Biol 5 (2007) e81
47. McStay B., and Grummt I. The epigenetics of rRNA genes: from molecular to chromosome biology. Annu Rev Cell Dev Biol 24 (2008) 131-157
48. Bourgeois C.A., Laquerriere F., Hemon D., Hubert J., and Bouteille M. New data on the in-situ position of the inactive X chromosome in the interphase nucleus of human fibroblasts. Hum Genet 69 (1985) 122-129
49. Bernardi R., and Pandolfi P.P. Structure, dynamics and functions of promyelocytic leukaemia nuclear bodies. Nat Rev Mol Cell Biol 8 12 (2007) 1006-1016
50. Lamond A.I., and Spector D.L. Nuclear speckles: a model for nuclear organelles. Nat Rev Mol Cell Biol 4 (2003) 605-612
51. Pandit S., Wang D., and Fu X.D. Functional integration of transcriptional and RNA processing machineries. Curr Opin Cell Biol 20 (2008) 260-265
52. Dillon N. The impact of gene location in the nucleus on transcriptional regulation. Dev Cell 15 (2008) 182-186
53. Kaiser T.E., Intine R.V., and Dundr M. De novo formation of a subnuclear body. Science 322 (2008) 1713-1717