Cell-of-Origin-Specific 3D Genome Structure Acquired during Somatic Cell Reprogramming

Krijger, Peter H.L.; Stefano, Bruno Di; Wit, Elzo de; Limone, Francesco; Oevelen, Chris van; Laat, Wouter de; Graf, Thomas

doi:10.1016/j.stem.2016.01.007

Cited by 171 publications

(152 citation statements)

References 38 publications

(69 reference statements)

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“…The bottom left Hi-C panel was created using the Juicebox software (Rao et al 2014). The top right Hi-C panel is reprinted from Krijger et al (2016). probes to target contact analysis to specific genomic sites. 3C-based methods are now becoming a routine tool in laboratories studying topics as diverse as gene regulation, replication, chromatin, and epigenetics.…”

Section: Early Discoveries Made By 3c Methodologiesmentioning

confidence: 99%

“…Polycomb group protein-bound regions such as the Hox genes spatially cluster in the nuclear space of ESCs (Denholtz et al 2013;Vieux-Rochas et al 2015), possibly even forming a spatial network with other developmental genes that are silenced but poised to be activated upon differentiation . Furthermore, TADs that are rich in binding sites for key pluripotency factors cluster in ESC nuclei Zhang et al 2013), as do regions in somatic cells that efficiently recruit their corresponding cellular identity factors (Lin et al 2012;Krijger et al 2016). These configurations are lost during differentiation (Dixon et al 2015) and reprogramming.…”

Section: Nuclear Positioning Of Tadsmentioning

confidence: 99%

“…Upon reprogramming of NSCs to induced pluripotent cells, the spatial network between NSC-specific SOX2-binding sites is dissolved and replaced by a configuration that brings together pluripotent-specific binding sites of SOX2 (see also Fig. 6; Krijger et al 2016). …”

Section: Nuclear Positioning Of Tadsmentioning

confidence: 99%

“…Using PE-SCAn, it was found that chromosomal regions that accumulate cellular identity factors such the pluripotency factors Nanog, Oct4, and Sox2 or the B-cell identity factor PU-1 cluster specifically in the corresponding cell types (Fig. 6;de Wit et al 2013;Krijger et al 2016).…”

Section: Hi-c Data Analysismentioning

confidence: 99%

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The second decade of 3C technologies: detailed insights into nuclear organization

2016

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The relevance of three-dimensional (3D) genome organization for transcriptional regulation and thereby for cellular fate at large is now widely accepted. Our understanding of the fascinating architecture underlying this function is based on microscopy studies as well as the chromosome conformation capture (3C) methods, which entered the stage at the beginning of the millennium. The first decade of 3C methods rendered unprecedented insights into genome topology. Here, we provide an update of developments and discoveries made over the more recent years. As we discuss, established and newly developed experimental and computational methods enabled identification of novel, functionally important chromosome structures. Regulatory and architectural chromatin loops throughout the genome are being cataloged and compared between cell types, revealing tissue invariant and developmentally dynamic loops. Architectural proteins shaping the genome were disclosed, and their mode of action is being uncovered. We explain how more detailed insights into the 3D genome increase our understanding of transcriptional regulation in development and misregulation in disease. Finally, to help researchers in choosing the approach best tailored for their specific research question, we explain the differences and commonalities between the various 3C-derived methods.

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Section: Early Discoveries Made By 3c Methodologiesmentioning

confidence: 99%

Section: Nuclear Positioning Of Tadsmentioning

confidence: 99%

Section: Nuclear Positioning Of Tadsmentioning

confidence: 99%

Section: Hi-c Data Analysismentioning

confidence: 99%

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The second decade of 3C technologies: detailed insights into nuclear organization

2016

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“…TADs determine distinct 3D chromosome structures based on the cell type origin. 25 Altering the structure of TADs and boundaries can lead to diseases. 24 Notably, 3D genome structure modifications play a central role in cell identity determination for other mechanisms such as transcriptional and epigenetic control, the details of which will be expanded in the following sections.…”

Section: Chromosomal Conformation Codementioning

confidence: 99%

Cellular identity at the single-cell level

2016

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A single cell creates surprising heterogeneity in a multicellular organism. While every organismal cell shares almost an identical genome, molecular interactions in cells alter the use of DNA sequences to modulate the gene of interest for specialization of cellular functions. Each cell gains a unique identity through molecular coding across the DNA, RNA, and protein conversions. On the other hand, loss of cellular identity leads to critical diseases such as cancer. Most cell identity dissection studies are based on bulk molecular assays that mask differences in individual cells. To probe cell-to-cell variability in a population, we discuss single cell approaches to decode the genetic, epigenetic, transcriptional, and translational mechanisms for cell identity formation. In combination with molecular instructions, the physical principles behind cell identity determination are examined. Deciphering and reprogramming cellular types impact biology and medicine.

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Cell-of-Origin-Specific 3D Genome Structure Acquired during Somatic Cell Reprogramming

Cited by 171 publications

References 38 publications

The second decade of 3C technologies: detailed insights into nuclear organization

The second decade of 3C technologies: detailed insights into nuclear organization

Cellular identity at the single-cell level

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