Loop stacking organizes genome folding from TADs to chromosomes

Hafner, Antonina; Park, Minhee; Berger, Scott E.; Nora, Elphège P.; Boettiger, Alistair N.

doi:10.1101/2022.07.13.499982

2022

DOI: 10.1101/2022.07.13.499982

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Loop stacking organizes genome folding from TADs to chromosomes

Antonina Hafner

¹

,

Minhee Park

²

,

Scott E. Berger

³

et al.

Abstract: While population level analyses reveal significant roles for CTCF and cohesin in mammalian genome organization, their contribution to chromatin structure and gene regulation at the single-cell level remain incompletely understood. Here, we use chromosome tracing microscopy to measure the effects of removal of CTCF or cohesin on genome folding across genomic scales. We find cohesin contracts the chromosome into loops, facilitating contacts both within and between Topologically Associating Domains (TADs), while … Show more

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Cited by 34 publications

(46 citation statements)

References 96 publications

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“…It is also worth noting that ChromSTEM imaging captures the statistics of single cell organizational states, whereas the ensemble measurement of Hi-C is an aggregate statistic of many organizational states. Consequently, this suggested that mature packing domains were largely maintained independent of cohesin mediated loop formation but that the principal effect of RAD21 extrusion was on the production of a subset of nascent domains, possibly consistent with findings in prior reports using oligo-based methods( 20, 22 ).…”

Section: Resultssupporting

confidence: 88%

Chromatin packing domains persist after RAD21 depletion in 3D

Li

¹

,

Carter

²

,

Almassalha

³

et al. 2024

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

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“…It is also worth noting that ChromSTEM imaging captures the statistics of single cell organizational states, whereas the ensemble measurement of Hi-C is an aggregate statistic of many organizational states. Consequently, this suggested that mature packing domains were largely maintained independent of cohesin mediated loop formation but that the principal effect of RAD21 extrusion was on the production of a subset of nascent domains, possibly consistent with findings in prior reports using oligo-based methods( 20, 22 ).…”

Section: Resultssupporting

confidence: 88%

Chromatin packing domains persist after RAD21 depletion in 3D

Li

¹

,

Carter

²

,

Almassalha

³

et al. 2024

Preprint

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…This indicates that enhancer-promoter hubs, which had so far only been described at high-resolution in a few selected loci 44,45 , are a common structural property of tissue-specific gene loci. Consistent with previous analyses based on multi-way 3C 45 and imaging expriments 77 , we also observe cooperative interactions between multiple CBSs, which likely reflect stacking of CBS-anchored loops into rosette structures. Notably, we also observe multi-way interactions involving enhancers, promoters, and CBSs, which is consistent with the promiscuous interaction patterns detected by MCC.…”

Section: Discussionsupporting

confidence: 90%

“…Computational modelling of our data indicates that cooperative interactions between CBSs form as a result of cohesin-mediated loop extrusion. A relatively high density of extruding cohesin molecules and relatively stable stalling of cohesin at CBSs are in principle sufficient to explain the clustering of CBSs at the bases of multiple extruded loops, consistent with previously described rosette structures and CTCF clusters 45,77,86 . Cohesin also stalls at enhancers and promoters, which may depend on interactions with Mediator 58,71,72 and RNA Polymerase II (RNAPII) 87–90 .…”

Section: Discussionsupporting

confidence: 87%

CTCF depletion decouples enhancer-mediated gene activation from chromatin hub formation during cellular differentiation

Karpińska

¹

,

Zhu

²

,

Ghazvini

³

et al. 2024

Preprint

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…S17). This increase in segment end-to-end distances and the continued presence of packing domains is consistent with chromatin tracing data [12,61]. Meanwhile, for separations less than 10 kb, there are only minor changes to contact frequencies, segment end-to-end distances, and clutch sizes.…”

Section: Discussionsupporting

confidence: 87%

Euchromatin forms condensed domains with short active regions on the surface

Paggi

¹

,

Zhang

²

2025

Preprint

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0

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

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