Menu

Close

Heterochromatin drives organization of conventional and inverted nuclei

Martin Falk, Yana Feodorova, Natasha Naumova, Maxim Imakaev, Bryan R. Lajoie, Heinrich Leonhardt, Boris Joffe, Job Dekker, Geoffrey Fudenberg, Irina Solovei, Leonid Mirny

Preprint posted on January 09, 2018 https://www.biorxiv.org/content/early/2018/01/09/244038

How is chromatin organized in 3D inside the nucleus? A new preprint uses Hi-C and microscopy to show the leading role of heterochromatin-driven phase separation and anchoring to the nuclear lamina in this process

Selected by Boyan Bonev


Why is it important?

3D chromatin organization is a key mechanism to regulate gene expression and cell fate. At the megabase scale, the genome is segmented into distinct topological units called domains or TADs; recent work has provided many lines of evidence that a cohesin-based mechanism of loop extrusion is essential for this level of organization. However, how distant regions with similar epigenetic nature interact in the 3D space of the nucleus to form higher-order structures called compartments is still unclear.

What are the key findings? 

In this preprint Mirny and colleagues explore the 3D nuclear architecture of rod photoreceptors, which are characterized by a peculiar inverted architecture with heterochromatin located in the nuclear core and euchromatin in the periphery. With a combination of microscopy and Hi-C based approaches they determined that the segregation into active/inactive compartments appears surprisingly unaffected in rod photoreceptors, despite the inversion evident by microscopy (Figure 1). Using polymer modeling and timecourse experiments they were able to show that compartmentalization in the nucleus is driven primarily by heterochromatin regions and surprisingly does not depend on interactions with the lamina or contacts between euchromatin regions. These results indicate that the inverted morphology of rod photoreceptor cells represents the default state of chromatin organization and additional mechanisms, such as the lamina anchoring of heterochromatin, are necessary to obtain the 3D nuclear architecture evident in most eukaryotic cells.

Figure 1. Rod neurons display inverted nuclear architecture by microscopy (A), but normal compartmentalization by Hi-C (B)   (Falk et al., bioRxiv 2018)

Questions arising

  1. Why do most cells have conventional topology (periphery-anchored heterochromatin) if it is dispensable for compartmentalization?
  2. Is heterochromatin aggregation driven by phase separation?
  3. How is compartmentalization affected in other cells with unconventional nuclear morphology (like plasma cells)?

Related Research

Solovei, I., et. al. & Joffe, B. LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation. Cell 152, 584–598 (2013).
Solovei, I. et al. Nuclear architecture of rod photoreceptor cells adapts to vision in mammalian evolution. Cell 137, 356–368 (2009).
Dekker, J. & Mirny, L. Perspective. Cell 164, 1110–1121 (2016).

Tags: 3d genome, chromatin, epigenetics, neurons, nuclear architecture

Posted on: 19th February 2018

Read preprint (No Ratings Yet)




  • Have your say

    Your email address will not be published. Required fields are marked *

    Sign up to customise the site to your preferences and to receive alerts

    Register here

    Also in the cell biology category:

    The cytoskeleton as a smart composite material: A unified pathway linking microtubules, myosin-II filaments and integrin adhesions

    Nisha Mohd Rafiq, Yukako Nishimura, Sergey V. Plotnikov, et al.



    Selected by Coert Margadant

    Quantitative, real-time, single cell analysis in tissue reveals expression dynamics of neurogenesis

    Cerys S Manning, Veronica Biga, James Boyd, et al.



    Selected by Teresa Rayon

    Profiling the surface proteome identifies actionable biology for TSC1 mutant cells beyond mTORC1 signaling

    Junnian Wei, Kevin K. Leung, Charles Truillet, et al.



    Selected by Rob Hynds

    1

    Optogenetic dissection of mitotic spindle positioning in vivo

    Lars-Eric Fielmich, Ruben Schmidt, Daniel J Dickinson, et al.



    Selected by Angika Basant

    1

    Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo.

    Jonathan B Michaux, Francois B Robin, William M McFadden, et al.



    Selected by Sundar Naganathan

    Moving beyond P values: Everyday data analysis with estimation plots

    Joses Ho, Tayfun Tumkaya, Sameer Aryal, et al.



    Selected by Gautam Dey

    1

    A limited number of double-strand DNA breaks are sufficient to delay cell cycle progression.

    Jeroen van den Berg, Anna G. Manjon, Karoline Kielbassa, et al.



    Selected by Leighton Daigh

    Optogenetic manipulation of medullary neurons in the locust optic lobe

    Hongxia Wang, Richard B. Dewell, Markus U. Ehrengruber, et al.



    Selected by Ana Patricia Ramos

    JNK-mediated spindle reorientation in stem cells promotes dysplasia in the aging intestine

    Daniel Hu, Heinrich Jasper



    Selected by Maiko Kitaoka

    ER-to-Golgi trafficking of procollagen in the absence of large carriers.

    Janine McCaughey, Nicola Stevenson, Stephen Cross, et al.



    Selected by Gautam Dey

    1

    Template switching causes artificial junction formation and false identification of circular RNAs

    Chong Tang, Tian Yu, Yeming Xie, et al.



    Selected by Fabio Liberante

    Mechanosensitive binding of p120-Catenin at cell junctions regulates E-Cadherin turnover and epithelial viscoelasticity

    K. Venkatesan Iyer, Romina Piscitello-Gómez, Frank Jülicher, et al.



    Selected by Ivana Viktorinová

    Targeting light-gated chloride channels to neuronal somatodendritic domain reduces their excitatory effect in the axon

    Jessica Messier, Hongmei Chen, Zhao-Lin Cai, et al.

    AND

    High-efficiency optogenetic silencing with soma-targeted anion-conducting channelrhodopsins

    Mathias Mahn, Lihi Gibor, Katayun Cohen-Kashi Malina, et al.



    Selected by Mahesh Karnani

    2

    EFFECTORS OF THE SPINDLE ASSEMBLY CHECKPOINT BUT NOT THE MITOTIC EXIT NETWORK ARE CONFINED WITHIN THE NUCLEUS OF SACCHAROMYCES CEREVISIAE

    Lydia R Heasley, Jennifer G DeLuca, Steven M Markus



    Selected by Hiral Shah

    An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics

    Ilias Angelidis, Lukas M Simon, Isis E Fernandez, et al.



    Selected by Rob Hynds

    1

    Peculiar features of the plastids of the colourless alga Euglena longa and photosynthetic euglenophytes unveiled by transcriptome analyses

    Kristina Zahonova, Zoltan Fussy, Erik Bircak, et al.



    Selected by Ellis O'Neill

    1

    Also in the genomics category:

    LADL: Light-activated dynamic looping for endogenous gene expression control

    Mayuri Rege, Ji Hun Kim, Jacqueline Valeri, et al.



    Selected by Ivan Candido-Ferreira

    Precise tuning of gene expression output levels in mammalian cells

    Yale S. Michaels, Mike B Barnkob, Hector Barbosa, et al.



    Selected by Tim Fessenden

    1

    Template switching causes artificial junction formation and false identification of circular RNAs

    Chong Tang, Tian Yu, Yeming Xie, et al.



    Selected by Fabio Liberante

    The genomic basis of colour pattern polymorphism in the harlequin ladybird

    Mathieu Gautier, Junichi Yamaguchi, Julien Foucaud, et al.



    Selected by Fillip Port

    Widespread inter-individual gene expression variability in Arabidopsis thaliana

    Sandra Cortijo, Zeynep Aydin, Sebastian Ahnert, et al.



    Selected by Martin Balcerowicz

    Single-cell Map of Diverse Immune Phenotypes Driven by the Tumor Microenvironment

    Elham Azizi, Ambrose J. Carr, George Plitas, et al.



    Selected by Tim Fessenden

    Cell type-specific interchromosomal interactions as a mechanism for transcriptional diversity

    Adan Horta, Kevin Monahan, Lisa Bashkirova, et al.



    Selected by Boyan Bonev

    PDX Finder: A Portal for Patient-Derived tumor Xenograft Model Discovery

    Nathalie Conte, Jeremy Mason, Csaba Halmagyi, et al.



    Selected by Carmen Adriaens

    An atlas of silencer elements for the human and mouse genomes

    Naresh Doni Jayavelu, Ajay Jajodia, Arpit Mishra, et al.



    Selected by Rafael Galupa

    1

    Capturing the onset of PRC2-mediated repressive domain formation

    Ozgur Oksuz, Varun Narendra, Chul-Hwan Lee, et al.



    Selected by Boyan Bonev

    Heterochromatin drives organization of conventional and inverted nuclei

    Martin Falk, Yana Feodorova, Natasha Naumova, et al.



    Selected by Boyan Bonev

    The ancestral animal genetic toolkit revealed by diverse choanoflagellate transcriptomes

    Daniel Richter, Parinaz Fozouni, Michael Eisen, et al.



    Selected by Rafael Galupa

    Genome-wide selection scans integrated with association mapping reveal mechanisms of physiological adaptation across a salinity gradient in killifish

    Reid S. Brennan, Timothy M. Healy, Heather J. Bryant, et al.



    Selected by Andy Turko

    Precise temporal regulation of alternative splicing during neural development

    Sebastien M Weyn-Vanhentenryck, Huijuan Feng, Dmytro Ustianenko, et al.



    Selected by James Gagnon

    Also in the neuroscience category:

    Moving beyond P values: Everyday data analysis with estimation plots

    Joses Ho, Tayfun Tumkaya, Sameer Aryal, et al.



    Selected by Gautam Dey

    1

    Optogenetic manipulation of medullary neurons in the locust optic lobe

    Hongxia Wang, Richard B. Dewell, Markus U. Ehrengruber, et al.



    Selected by Ana Patricia Ramos

    Targeting light-gated chloride channels to neuronal somatodendritic domain reduces their excitatory effect in the axon

    Jessica Messier, Hongmei Chen, Zhao-Lin Cai, et al.

    AND

    High-efficiency optogenetic silencing with soma-targeted anion-conducting channelrhodopsins

    Mathias Mahn, Lihi Gibor, Katayun Cohen-Kashi Malina, et al.



    Selected by Mahesh Karnani

    2

    Phenotypic landscape of schizophrenia-associated genes defines candidates and their shared functions

    Summer B. Thyme, Lindsey M. Pieper, Eric H. Li, et al.



    Selected by Daniel Grimes

    Cerebellar contribution to preparatory activity in motor neocortex

    Francois Pierre Chabrol, Antonin Blot, Thomas D Mrsic-Flogel



    Selected by Mahesh Karnani

    1

    Fbxw7 is a critical regulator of Schwann cell myelinating potential

    Breanne L Harty, Fernanda Coelho, Sarah D Ackerman, et al.



    Selected by Yen-Chung Chen

    OptoGranules reveal the evolution of stress granules to ALS-FTD pathology

    Peipei Zhang, Baochang Fan, Peiguo Yang, et al.



    Selected by Srivats Venkataramanan

    1

    Mouse dLGN receives input from a diverse population of retinal ganglion cells with limited convergence

    Miroslav Román Rosón, Yannik Bauer, Philipp Berens, et al.



    Selected by Polona Jager

    Sparse recurrent excitatory connectivity in the microcircuit of the adult mouse and human cortex

    Stephanie C Seeman, Luke Campagnola, Pasha A Davoudian, et al.



    Selected by Mahesh Karnani

    1

    Cell type-specific interchromosomal interactions as a mechanism for transcriptional diversity

    Adan Horta, Kevin Monahan, Lisa Bashkirova, et al.



    Selected by Boyan Bonev

    Feedback control of neurogenesis by tissue packing

    Tom W. Hiscock, Joel B. Miesfeld, Kishore R. Mosaliganti, et al.



    Selected by Sarah Morson

    1

    Heterochromatin drives organization of conventional and inverted nuclei

    Martin Falk, Yana Feodorova, Natasha Naumova, et al.



    Selected by Boyan Bonev

    GSK3 Controls Migration of the Neural Crest Lineage

    Sandra G Gonzalez Malagon, Anna Lopez Munoz, Daniel Doro, et al.



    Selected by Amanda Haage
    Close