Chromatin Architecture Reorganization during Stem Cell Differentiation

By Jesse R. Dixon, Inkyung Jung, Siddarth Selvaraj, Yin Shen, Jessica Antosiewicz-Bourget, A. Lee, Z. Ye, Audrey Kim, N. Rajagopal, Wei Xie and 7 more. Nature, 2015

1,540 citations recorded by the source corpus.

Higher-order chromatin structure is emerging as an important regulator of gene expression. Although dynamic chromatin structures have been identified in the genome, the full scope of chromatin dynamics during mammalian development and lineage specification remains to be determined. By mapping genome-wide chromatin interactions in human embryonic stem (ES) cells and four human ES-cell-derived lineages, we uncover extensive chromatin reorganization during lineage specification. We observe that although self-associating chromatin domains are stable during differentiation, chromatin interactions both within and between domains change in a striking manner, altering 36% of active and inactive chromosomal compartments throughout the genome. By integrating chromatin interaction maps with haplotype-resolved epigenome and transcriptome data sets, we find widespread allelic bias in gene expression correlated with allele-biased chromatin states of linked promoters and distal enhancers. Our results therefore provide a global view of chromatin dynamics and a resource for studying long-range control of gene expression in distinct human cell lineages.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/60dbfd78e66aa78cd6bb106861640eedf1a7aa10

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Citations in the corpus

Revealing the vectors of cellular identity with single-cell genomics (2016, background): “In particular, once haplotypes are resolved 195–197 , single-cell epigenomic profiles should allow correlation of events such as the methylation patterns of a gene’s promoters and enhancers, or of enhancers targeted by the same transcription factor 198 .”
Genome-wide mapping and analysis of chromosome architecture (2016, background): “Interestingly, this large-scale genome compart-mentalization is highly dynamic during the differentiation of human embryonic stem cells 62 and between normal and cancer cells 22 , suggesting compartmentalization has a crucial role in mediating genome function and cell identity.”
HiCRep: assessing the reproducibility of Hi-C data using a stratum-adjusted correlation coefficient (2017, positive): “We generated the Hi-C contact matrices using the pipeline from Dixon et al. (2015).”
The Post-GWAS Era: From Association to Function. (2018, background): “, 4C or Hi-C), designing the experiment such that haplotype marker SNPs are present in the sequenced ligation products.(79,81,82) In an example of the former approach, Stadhouders et al.”
Predicting enhancer-promoter interaction from genomic sequence with deep neural networks (2016, background): “Distal regulatory enhancer elements in the genome can interact with proximal promoter regions to regulate the target gene’s expression, and mutations that change such interactions will cause the target gene to be dysregulated [6, 11, 34].”
Exploring Epigenomic Datasets by ChIPseeker (2022, methodology): “As an example, we have used re-analyzed CTCF ChIP-seq results in BED format, which were deposited in the NCBI database under accession number GSE52457 (Dixon et al., 2015).”
The 3D Genome Browser: a web-based browser for visualizing 3D genome organization and long-range chromatin interactions (2017, methodology): “All the Hi-C matrices in this manuscript are converted to BUTLR file format for visualization [5, 8, 19, 20, 22 – 24”
CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function (2015, positive): “Finally, we performed Hi-C experiments on SK-N-SH and analyzed the results along with previously published Hi-C data from H1-hESC and NPC cells (Dixon et al., 2012, 2015) (Figure S1J).”