A Cascade of Histone Modifications Induces Chromatin Condensation in Mitosis

Wilkins, Bryan J.; Rall, Nils Arne; Ostwal, Yogesh B.; Kruitwagen, Tom; Hiragami-Hamada, Kyoko; Winkler, Marco; Barral, Yves; Fischle, Wolfgang; Neumann, Heinz

doi:10.1126/science.1244508

Cited by 244 publications

(278 citation statements)

References 33 publications

Supporting

Mentioning

263

Contrasting

Order By: Relevance

“…The type of interactions at the range of <20 kb of DNA revealed by our EM-assisted nucleosome capture experiments and modeling suggest a global nucleosome array condensation mechanism: in mitosis, the loop size would be modulated by factors promoting frequency of loop formation along the chromosome axis such as condensin (30,37) as well as chromatin fiber flexibility and interdigitation such as decreased linker histone affinity (38), metaphase-specific histone modifications (42), and increased divalent cation association (43). Further experimental and modeling studies of nucleosome interactions using high-resolution multiscale computational approaches (2,44) are essential for connecting chromatin's structural and epigenetic states.…”

Section: Discussionmentioning

confidence: 99%

Hierarchical looping of zigzag nucleosome chains in metaphase chromosomes

Grigoryev

Bascom

Buckwalter

et al. 2016

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

126

174

View full text Add to dashboard Cite

The architecture of higher-order chromatin in eukaryotic cell nuclei is largely unknown. Here, we use electron microscopy-assisted nucleosome interaction capture (EMANIC) cross-linking experiments in combination with mesoscale chromatin modeling of 96-nucleosome arrays to investigate the internal organization of condensed chromatin in interphase cell nuclei and metaphase chromosomes at nucleosomal resolution. The combined data suggest a novel hierarchical looping model for chromatin higher-order folding, similar to rope flaking used in mountain climbing and rappelling. Not only does such packing help to avoid tangling and self-crossing, it also facilitates rope unraveling. Hierarchical looping is characterized by an increased frequency of higher-order internucleosome contacts for metaphase chromosomes compared with chromatin fibers in vitro and interphase chromatin, with preservation of a dominant two-start zigzag organization associated with the 30-nm fiber. Moreover, the strong dependence of looping on linker histone concentration suggests a hierarchical self-association mechanism of relaxed nucleosome zigzag chains rather than longitudinal compaction as seen in 30-nm fibers. Specifically, concentrations lower than one linker histone per nucleosome promote self-associations and formation of these looped networks of zigzag fibers. The combined experimental and modeling evidence for condensed metaphase chromatin as hierarchical loops and bundles of relaxed zigzag nucleosomal chains rather than randomly coiled threads or straight and stiff helical fibers reconciles aspects of other models for higher-order chromatin structure; it constitutes not only an efficient storage form for the genomic material, consistent with other genome-wide chromosome conformation studies that emphasize looping, but also a convenient organization for local DNA unraveling and genome access. chromatin higher-order structure | nucleosome | linker histone | mesoscale modeling | electron microscopy T he physical packaging of megabase pairs of genomic DNA stored as the chromatin fiber in eukaryotic cell nuclei has been one of the great challenges in biology (1). The limited resolution and disparate levels that can be studied by both experimental and modeling studies of chromatin, which exhibits multiple spatial and temporal scales par excellence, make it challenging to present an integrated structural view, from nucleosomes to chromosomes (2). Because all fundamental template-directed processes of DNA depend on chromatin architecture, advances in our understanding of chromatin higher-order organization are needed to help interpret numerous regulatory events from DNA damage repair to epigenetic control.At the primary structural level, the DNA makes ∼1.7 left-superhelical turns around eight core histones to form a nucleosome core. The nucleosome cores are connected by linker DNA to form nucleosome arrays. An X-ray crystal structure of the nucleosome core has been solved at atomic resolution (3), and a short, four-nucleosome array has also been ...

show abstract

Section: Discussionmentioning

confidence: 99%

Hierarchical looping of zigzag nucleosome chains in metaphase chromosomes

Grigoryev

Bascom

Buckwalter

et al. 2016

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

126

174

View full text Add to dashboard Cite

show abstract

“…Furthermore, histone modifications, such as global histone acetylation, which are associated with active gene expression, are generally diminished during mitosis (Kruhlak et al, 2001;. Loss of histone tail acetylation, such as H4K16, has been found to be directly linked to mitotic-specific histone phosphorylation (H3S10P), promoting chromatin fiber condensation (Wilkins et al, 2014). However, residual amounts of histone acetylation, which bookmarks a select group of gene promoters, has also been reported (Dey et al, 2009;Kouskouti and Talianidis, 2005;Valls et al, 2005;Zhao et al, 2011).…”

Section: Mitosis and Epigenetic Memorymentioning

confidence: 99%

Cycling through developmental decisions: how cell cycle dynamics control pluripotency, differentiation and reprogramming

2016

View full text Add to dashboard Cite

A strong connection exists between the cell cycle and mechanisms required for executing cell fate decisions in a wide-range of developmental contexts. Terminal differentiation is often associated with cell cycle exit, whereas cell fate switches are frequently linked to cell cycle transitions in dividing cells. These phenomena have been investigated in the context of reprogramming, differentiation and trans-differentiation but the underpinning molecular mechanisms remain unclear. Most progress to address the connection between cell fate and the cell cycle has been made in pluripotent stem cells, in which the transition through mitosis and G1 phase is crucial for establishing a window of opportunity for pluripotency exit and the initiation of differentiation. This Review will summarize recent developments in this area and place them in a broader context that has implications for a wide range of developmental scenarios.

show abstract

“…These marks are removed during mitotic exit by the phosphatase PP1, which is recruited to anaphase chromatin by its targeting cofactor RepoMan (also known as CDCA2) (Trinkle-Mulcahy et al, 2006) and mKI67 (Booth et al, 2014;Takagi et al, 2014). Although it has been recently proposed to be upstream of a histone modification cascade that promotes mitotic chromosome condensation (Wilkins et al, 2014), phosphorylation of histone H3 at S10 is dispensable for chromosome condensation (Hsu et al, 2000;MacCallum et al, 2002) and to date there is no evidence to suggest that the reversal of histone phosphorylation events are specifically required for chromatin decondensation at the end of mitosis (Magalska et al, 2014). Instead, chromatin remodelling downstream of histone dephosphorylation has been linked to nuclear envelope assembly by promoting the recruitment of LBR through heterochromatin protein 1β (HP1β) (Ye et al, 1997;Haraguchi et al, 2000;Fischle et al, 2005) and importin-β-bound nucleoporins through RepoMan (Vagnarelli et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

The lysine demethylase LSD1 is required for nuclear envelope formation at the end of mitosis

Schooley

Moreno-Andrés

Magistris

et al. 2015

Journal of Cell Science

View full text Add to dashboard Cite

The metazoan nucleus breaks down and reassembles during each cell division. Upon mitotic exit, the successful reestablishment of an interphase nucleus requires the coordinated reorganization of chromatin and formation of a functional nuclear envelope. Here, we report that the histone demethylase LSD1 (also known as KDM1A) plays a crucial role in nuclear assembly at the end of mitosis. Downregulation of LSD1 in cells extends telophase and impairs nuclear pore complex assembly. In vitro, LSD1 demethylase activity is required for the recruitment of MEL28 (also known as ELYS and AHCTF1) and nuclear envelope precursor vesicles to chromatin, crucial steps in nuclear reassembly. Accordingly, the formation of a closed nuclear envelope and nuclear pore complex assembly are impaired upon depletion of LSD1 or inhibition of its activity. Our results identify histone demethylation by LSD1 as a new regulatory mechanism linking the chromatin state and nuclear envelope formation at the end of mitosis.

show abstract

A Cascade of Histone Modifications Induces Chromatin Condensation in Mitosis

Cited by 244 publications

References 33 publications

Hierarchical looping of zigzag nucleosome chains in metaphase chromosomes

Hierarchical looping of zigzag nucleosome chains in metaphase chromosomes

Cycling through developmental decisions: how cell cycle dynamics control pluripotency, differentiation and reprogramming

The lysine demethylase LSD1 is required for nuclear envelope formation at the end of mitosis

Contact Info

Product

Resources

About