HiChIP: efficient and sensitive analysis of protein-directed genome architecture

Mumbach, Maxwell R.; Rubin, Adam J.; Flynn, Ryan A.; Dai, Chao; Khavari, Paul A.; Greenleaf, William J.; Chang, Howard Y.

doi:10.1038/nmeth.3999

Cited by 909 publications

(917 citation statements)

References 28 publications

(60 reference statements)

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“…Our 20kb resolution data (Figure 2A-B) did not allow us to perform robust de novo calling of loops. However, given that most CTCF binding events overlap with Cohesin enrichment by ChIP-seq (Parelho et al, 2008; Rubio et al, 2008; Wendt et al, 2008), we performed a meta-analysis by aggregating our Hi-C signal at CTCF/Cohesin bound loops, as previously detected by high-resolution HiChip for Smc1a in mESCs (Mumbach et al, 2016). This confirmed that CTCF is required for the interaction between CTCF/Cohesin bound loop-anchor loci genome-wide, and that bringing CTCF back is sufficient to restore these preferential contacts (Figure 2C).…”

Section: Resultsmentioning

confidence: 99%

“…We explored if this activator role may be attributed to CTCF facilitating communication with distal regulatory elements. Out of the 188 genes down-regulated after 1 day of depletion only 53 (28%) overlap an anchor for SMC1a HiChIP loops (Mumbach et al, 2016) and 19 (10%) connect to an active regulatory region before treatment, based on H3K27Ac enrichment (Shen et al, 2012). Furthermore, down-regulated genes are not specifically positioned at TAD boundaries.…”

Section: Resultsmentioning

confidence: 99%

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Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization

Nora

Goloborodko

Valton

et al. 2017

Cell

1,411

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Summary The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and insulation of topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding. CTCF remains essential for TAD organization in non-dividing cells. Surprisingly, active and inactive genome compartments remain properly segregated upon CTCF depletion, revealing that compartmentalization of mammalian chromosomes emerges independently of proper insulation of TADs. Further, our data support that CTCF mediates transcriptional insulator function through enhancer-blocking but not as a direct barrier to heterochromatin spreading. Beyond defining the functions of CTCF in chromosome folding these results provide new fundamental insights into the rules governing mammalian genome organization.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization

Nora

Goloborodko

Valton

et al. 2017

Cell

1,411

175

1,641

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“…The ease of experimental procedure and small amount of input materials required will allow the mapping of longrange chromatin interactions in a broad set of species, cell types, and experimental settings. A similar method called HiChIP was recently reported by Mumbach et al [15] when our manuscript was under review.…”

mentioning

confidence: 81%

Mapping of long-range chromatin interactions by proximity ligation-assisted ChIP-seq

et al. 2016

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“…These assays directly identify genomic loci that are in sufficiently close proximity in living cells to be cross‐linked 117. Several versions of 3C such as 4Cseq, ChIA‐PET,112 5C111 HiChIP118 and Hi‐C113 allow for mapping of chromatin interactions on a whole genome level. Recently, to improve the resolution and sensitivity of Hi‐C assays, in situ protocols have been developed.…”

Section: Mapping the 3d Genomementioning

confidence: 99%

Unravelling the molecular basis for regulatory T‐cell plasticity and loss of function in disease

et al. 2018

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Regulatory T cells (Treg) are critical for preventing autoimmunity and curtailing responses of conventional effector T cells (Tconv). The reprogramming of T‐cell fate and function to generate Treg requires switching on and off of key gene regulatory networks, which may be initiated by a subtle shift in expression levels of specific genes. This can be achieved by intermediary regulatory processes that include microRNA and long noncoding RNA‐based regulation of gene expression. There are well‐documented microRNA profiles in Treg and Tconv, and these can operate to either reinforce or reduce expression of a specific set of target genes, including FOXP3 itself. This type of feedforward/feedback regulatory loop is normally stable in the steady state, but can alter in response to local cues or genetic risk. This may go some way to explaining T‐cell plasticity. In addition, in chronic inflammation or autoimmunity, altered Treg/Tconv function may be influenced by changes in enhancer–promoter interactions, which are highly cell type‐specific. These interactions are impacted by genetic risk based on genome‐wide association studies and may cause subtle alterations to the gene regulatory networks controlled by or controlling FOXP3 and its target genes. Recent insights into the 3D organisation of chromatin and the mapping of noncoding regulatory regions to the genes they control are shedding new light on the direct impact of genetic risk on T‐cell function and susceptibility to inflammatory and autoimmune conditions.

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HiChIP: efficient and sensitive analysis of protein-directed genome architecture

Cited by 909 publications

References 28 publications

Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization

Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization

Mapping of long-range chromatin interactions by proximity ligation-assisted ChIP-seq

Unravelling the molecular basis for regulatory T‐cell plasticity and loss of function in disease

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