Genome organization at different scales: nature, formation and function

Serizay, Jacques; Ahringer, Julie

doi:10.1016/j.ceb.2018.03.009

Cited by 23 publications

(15 citation statements)

References 73 publications

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“…Spatial organization and dynamics of chromatin correlate with cell function and fate [1]. On the coarsest level, chromosomes occupy territories in mammalian cells [2].…”

Section: Introductionmentioning

confidence: 99%

Hi-D: nanoscale mapping of nuclear dynamics in single living cells

et al. 2020

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Bulk chromatin motion has not been analyzed at high resolution. We present HiD , a method to quantitatively map dynamics of chromatin and abundant nuclear proteins for every pixel simultaneously over the entire nucleus from fluorescence image series. HiD combines reconstruction of chromatin motion and classification of local diffusion processes by Bayesian inference. We show that DNA dynamics in the nuclear interior are spatially partitioned into 0.3-3-μm domains in a mosaic-like pattern, uncoupled from chromatin compaction. This pattern was remodeled in response to transcriptional activity. HiD can be applied to any dense and bulk structures opening new perspectives towards understanding motion of nuclear molecules.

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“…Spatial organization and dynamics of chromatin correlate with cell function and fate [1]. On the coarsest level, chromosomes occupy territories in mammalian cells [2].…”

Section: Introductionmentioning

confidence: 99%

Hi-D: nanoscale mapping of nuclear dynamics in single living cells

et al. 2020

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show abstract

“…Spatial organization and dynamics of chromatin correlate with cell function and fate [1]. In mammalian cells, chromosomes occupy territories whose localization is stable over the cell cycle [2].…”

Section: Introductionmentioning

confidence: 99%

Hi-D: Nanoscale mapping of nuclear dynamics in single living cells

Shaban

Barth

Bystricky

2018

Preprint

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ABSTRACTBulk chromatin motion has not been analysed at high resolution. We present Hi-D, a method to quantitatively map dynamics of chromatin and abundant nuclear proteins for every pixel simultaneously over the entire nucleus from fluorescence image series. Hi-D combines reconstruction of chromatin motion, and classification of local diffusion processes by Bayesian inference. We show that DNA dynamics in the nuclear interior are spatially partitioned into 0.3 – 3 μm domains in a mosaic-like pattern, uncoupled from chromatin compaction. This pattern was remodelled in response to transcriptional activity. Hi-D can be applied to any dense and bulk structures opening new perspectives towards understanding motion of nuclear molecules.

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“…The A compartment contains euchromatin, which is accessible, transcriptionally active, and marked by specific histone modifications, such as H3K4me3. The B compartment, which is more condensed, contains inactive genes, many repeated elements, and is associated with different histone modifications, including H3K9me3 13 . In addition to the structural distinctions, regions of the genome are also subject to temporal control of replication during S phase.…”

Section: Introductionmentioning

confidence: 99%

DONSON and FANCM associate with different replisomes distinguished by replication timing and chromatin domain

Zhang

Bellani

James

et al. 2020

Preprint

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25Duplication of mammalian genomes requires replisomes to overcome numerous impediments 26 during passage through open (eu) and condensed (hetero) chromatin. Typically, studies of 27 replication stress characterize mixed populations of challenged and unchallenged replication forks, 28 averaged across S phase, and model a single species of "stressed" replisome. However, in cells 29 containing potent obstacles to replication, we find two different lesion proximal replisomes. One 30 is bound by the DONSON protein and is more frequent in early S phase, in regions marked by 31 euchromatin. The other interacts with the FANCM DNA translocase, is more prominent in late S 32 phase, and favors heterochromatin. The two forms can also be detected in unstressed cells. CHIP-33 seq of DNA associated with DONSON or FANCM confirms the bias of the former towards regions 34 that replicate early and the skew of the latter towards regions that replicate late. 35Introduction 36 Eukaryotic replisomes are multiprotein complexes consisting, minimally, of the CMG 37 helicase [MCM2-7 (M), CDC45 (C), and GINS (go, ichi, ni, san) proteins (G)] which forms a ring 38 around the leading strand template. Other components include the pol α, ε, and δ polymerases, 39 MCM10, and a few accessory factors [1][2][3][4][5][6][7] . The identification and characterization of the minimal 40 components of biochemically active replisomes, the result of decades of extraordinary work from 41 multiple laboratories, necessarily reflects studies with deproteinized model DNA substrates under 42 carefully controlled conditions. However, in vivo there are hundreds of replisome associated 43 proteins 8-12 . Presumably this reflects the multiple layers of complexity that characterize replication 44 of the genome in living cells. For example, three dimensional analyses of chromosome structure 45 demonstrate two major domains. The A compartment contains euchromatin, which is accessible, 46 transcriptionally active, and marked by specific histone modifications, such as H3K4me3. The B 47 compartment, which is more condensed, contains inactive genes, many repeated elements, and is 48 associated with different histone modifications, including H3K9me3 13 . In addition to the structural 49 distinctions, regions of the genome are also subject to temporal control of replication during S 50 phase. Sequences in Compartment A tend to replicate early in S phase, while those in B are 51 duplicated in late S phase 14,15 . 52 Other influential effectors of replisome composition are the frequent encounters with 53 impediments, that stall or block either the progress of the CMG helicase or DNA synthesis. These 54 3 include alternate DNA structures, protein: DNA adducts, DNA covalent modifications introduced 55 by endogenous or endogenous reactants, depleted nucleotide precursor pools, etc. Replication 56 stress activates the ATR (ATM-and Rad3-related) kinase, with hundreds of substrates, including 57 MCM proteins [16][17][18] , and stimulates the recruitment of numerous facto...

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Genome organization at different scales: nature, formation and function

Cited by 23 publications

References 73 publications

Hi-D: nanoscale mapping of nuclear dynamics in single living cells

Hi-D: nanoscale mapping of nuclear dynamics in single living cells

Hi-D: Nanoscale mapping of nuclear dynamics in single living cells

DONSON and FANCM associate with different replisomes distinguished by replication timing and chromatin domain

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