Human Biology & BioImaging
print


Breadcrumb Navigation


Content

Research Group Solovei

Research Group Solovei


The position of genes in relation to eu- and heterochromatin domains as well as to other gene loci, plays an important role in the regulation of transcriptional activity. Our group studies the mechanisms underlying the establishment of epigenetic landscape of the mammalian nuclei, in particular, mechanisms of positional regulation of chromosomal loci.

Spatial segregation of transcriptionally active euchromatin and silent heterochromatin is an important factor regulating nuclear functions. Most eukaryotic nuclei have conventional architecture with ag_solovei_image_1transcriptionally active euchromatin residing in the nuclear interior and heterochromatin abutting the nuclear periphery and the nucleolus. Recently, we found a unique exception to the above rule, in nuclei of rod photoreceptor cells of nocturnal mammals. For optical reasons, heterochromatin is concentrated in the center of these nuclei whereas euchromatin lines the nuclear periphery, thereby forming an inverted nuclear organization in comparison to conventional nuclei.

ag_solovei_image_2Mammalian chromosomes consist of alternating segments of eu- and heterochromatin roughly corresponding to R- and C/G-bands, respectively. In both conventional and inverted nuclei, chromosomes acquire a complex folded structure which adapts to the shape of the nucleus and secures correct intranuclear positioning of eu- and heterochromatin regions. Mechanisms of chromosome folding and factors defining peripheral versus internal positioning of heterochromatin remain largely unknown. We aim to uncover these mechanisms.


Related papers:

Solovei I, Kreysing M, Lanctot C, Koesem S, Peichl L, Cremer T, Guck J and Joffe B (2009). Nuclear Architecture of Rod Photoreceptor Cells Adapts to Vision in Mammalian Evolution. Cell, 137, 356-368

Joffe B, Leonhardt H and Solovei I (2010). Differentiation and large scale spatial organization of the genome. Curr Opin Gen Dev, 20, 562-569

Solovei I and Joffe B (2010). Inverted nuclear architecture and its development during differentiation of mouse rod photoreceptor cells: a new model to study nuclear architecture. Genetika, 46, 1159-1163 

top


Inverted nuclear architecture of rod photoreceptors as a model to study general
mechanisms of chromosome folding in the nucleus.


The mouse rod nucleus is a convenient model to study epigenetic marks that might be involved in the formation of the inverted nuclear architecture. In their nuclei, the main chromatin classes occupy spatially separated consecutive shells which strongly simplifies evaluation of the intranuclear signal distribution. We have performed an extensive ag_solovei_image_3immunostaining assay of the epigenetic landscape of mouse rod nuclei but have not found differences in epigenetic markers characteristic of eu- and heterochromatin in both nuclear types.

ag_solovei_image_4Recently, we identified LBR- and lamin-A/C-dependent mechanisms tethering heterochromatin to the nuclear envelope. The two tethers are sequentially used during cellular differentiation and development: first the LBR- and then the lamin-A/C-dependent tether. The absence of both LBR and lamin A/C leads to loss of peripheral heterochromatin and an inverted architecture with heterochromatin localizing to the nuclear interior. Myoblast transcriptome analyses indicated that selective disruption of the LBR- or lamin-A-dependent heterochromatin tethers have opposite effects on muscle gene expression, by either increasing or decreasing transcription of the genes, respectively. These results show how changes in nuclear envelope composition contribute to regulating heterochromatin positioning, gene expression, and cellular differentiation during development.

Available data suggest that several nuclear envelope transmembrane proteins (LEM-domain proteins, in the first place) are involved in anchoring peripheral heterochromatin by a lamin A/C-dependent tether. We aim to identify these proteins and we attach a great importance to this study because the analysis of rods can strongly contribute to understanding of cardinal biological problems related to spatial transcriptional regulation, as well as of medical problems associated with the whole spectrum of laminopathies.


Related papers:

Eberhart A, Feodorova Y, Song C, Wanner G, Kiseleva E, Furukawa T, Kimura H, Schotta G, Leonhardt H, Joffe B and Solovei I (2013). Epigenetics of eu- and heterochromatin in inverted and conventional nuclei from mouse retina. Chromosome Res, 21, 535-554

Solovei I, Wang AS, Thanisch K, Schmidt CS, Krebs S, Zwerger M, Cohen TV, Devys D, Foisner R, Peichl L, Herrmann H, Blum H, Engelkamp D, Stewart CL, Leonhardt H and Joffe B (2013). LBR and Lamin A/C Sequentially Tether Peripheral Heterochromatin and Inversely Regulate Differentiation. Cell, 152, 584-598

Song C, Feodorova Y, Guy J, Peichl L, Jost KL, Kimura H, Cardoso MC, Bird A, Leonhardt H, Joffe B, Solovei I. 2014 DNA methylation reader MECP2: cell type- and differentiation stage-specific protein distribution. Epigenetics & Chromatin, 7, 17

top 

Functional organization of rod nuclei, ecology, ethology and the evolution of mammals


ag_solovei_image_5We aim to correlate evolution of lifestyle with evolution of vision in a number of mammalian groups. Currently we are collecting retinal material to fill gaps in the mammalian evolutionary tree. The analysis includes immunostaining of retinal cryosections for histone modifications and nuclear lamina proteins. Mammals with inverted rod nuclei express neither LamA/C nor LBR, whereas all mammals with a conventional chromatin pattern express either LBR or LamA/C. Because the transition from nocturnal to diurnal lifestyle occurred in a number of mammalian taxa, each of the two proteins was independently reacquired several times.


Related papers:

Solovei I, Kreysing M, Lanctot C, Koesem S, Peichl L, Cremer T, Guck J and  Joffe B (2009). Nuclear Architecture of Rod Photoreceptor Cells Adapts to Vision in Mammalian Evolution. Cell, 137, 356-368

Solovei I, Wang AS, Thanisch K, Schmidt CS, Krebs S, Zwerger M, Cohen TV, Devys D, Foisner R, Peichl L, Herrmann H, Blum H, Engelkamp D, Stewart CL, Leonhardt H and Joffe B (2013). LBR and Lamin A/C Sequentially Tether Peripheral Heterochromatin and Inversely Regulate Differentiation. Cell, 152, 584-598

top 

Diurnality and nocturnality in primates: An analysis from the rod photoreceptor nuclei perspective
 

Diurnality, associated with enhanced visual acuity and color vision, is typical of most modern primates. However, it remains a matter of debate when and how many times primates re-acquired diurnality or returned to nocturnality. We analyzed the features specific to nocturnal and diurnal vision that were recently found in the nuclei of mammalian rod photoreceptor cells in 11 species representing various groups of the primates as well as the related tree shrew and colugo.

ag_solovei_image_6Heterochromatin in rod nuclei of nocturnal primates is clustered in the center of rod nuclei (inverted architecture), whereas rods of diurnal mammals retain rods with peripheral heterochromatin (conventional architecture). Rod nuclei of the nocturnal owl monkey have a state transitional to the inverted one. Surprisingly, rod nuclei of the tarsier have a conventional nuclear architecture typical for diurnal mammals, strongly implying that recent Tarsiiformes returned to nocturnality from the diurnal state. Diurnal lemurs retain inverted rod nuclei typical of nocturnal mammals, which conforms to the notion that the ancestors of all Lemuroidea were nocturnal. Data on the expression of proteins indispensable for peripheral heterochromatin maintenance in rod cells support the view that the primate ancestors were nocturnal and transition to diurnality occurred independently in several primate and related groups: Tupaia, diurnal lemurs, and, at least partially independently, in Simiiformes (monkeys and apes) and Tarsiiformes.


Related papers:

Kuhrt H, Gryga M, Wolburg H, Joffe B, Grosche J, Reichenbach A and Noori HR (2012). Postnatal mammalian retinal development: quantitative data and general rules. Prog Retin Eye Res, 31, 605-621

Joffe B, Peichl L, Hendrickson A, Leonhardt H and Solovei I (2014). Diurnality and Nocturnality in Primates: An Analysis from the Rod Photoreceptor Nuclei Perspective. Evol Biol, 41, 1-11

 top

Some methodological papers from our group:

Ronneberger O, Baddeley D, Scheipl F, Verveer PJ, Burkhardt H, Cremer C, Fahrmeir L, Cremer T and Joffe B (2008). Spatial quantitative analysis of fluorescently labeled nuclear structures: problems, methods, pitfalls. Chromosome Res, 16, 523-562

Solovei I (2010). Fluorescence in situ hybridization (FISH) on tissue cryosections. Methods Mol Biol. 659, 71-82 

Solovei  I and Cremer M (2010). 3D-FISH on cultured cells combinedwith immunostaining. Methods Mol Biol. 659, 117-26

Eberhart A, Kimura H, Leonhardt H, Joffe B and Solovei I (2012). Reliable detection of epigenetic histone marks and nuclear proteins in tissue cryosections. Chromosome Res., 20, 849-58

Feodorova Y, Koch M, Bultmann S, Michalakis S and Solovei I (2015). Quick and reliable method for retina dissociation and separation of rod photoreceptor perikarya from adult mice. MethodsX, 2, 39-46.

 

                            

boris_joffe_9x11-300All of the above projects were initiated and carried out together with Dr. Boris Joffe (01.03.1953-15.01.2014), a genuine and passionate scientist.