Genomics

Dataset Information

168

YY1 and CTCF Orchestrate a 3D Chromatin Looping Switch during Early Neural Lineage Commitment


ABSTRACT: CTCF is an architectural protein with a critical role in connecting higher-order chromatin folding in pluripotent stem cells. Recent reports have suggested that CTCF binding is more dynamic during development than previously appreciated. Here we set out to understand the extent to which shifts in genome-wide CTCF occupancy contribute to the 3-D reconfiguration of fine-scale chromatin folding during early neural lineage commitment. Unexpectedly, we observe a sharp decrease in CTCF occupancy during the transition from naïve/primed pluripotency to multipotent primary neural progenitor cells (NPCs). Many pluripotency gene-enhancer interactions are anchored by CTCF and its occupancy is lost in parallel with loop decommissioning during differentiation. Conversely, CTCF binding sites in NPCs are largely pre-existing in pluripotent stem cells. Only a small number of CTCF sites arise de novo in NPCs. We identify another zinc finger protein, Yin Yang 1 (YY1), at the base of looping interactions between NPC-specific genes and enhancers. Putative NPC-specific enhancers exhibit strong YY1 signal when engaged in 3-D contacts and negligible YY1 signal when not in loops. Moreover, siRNA knockdown of YY1 specifically disrupts interactions between key NPC enhancers and their target genes. YY1-mediated interactions between NPC regulatory elements are often nested within constitutive loops anchored by CTCF. Together, our results support a model in which YY1 acts as an architectural protein to connect developmentally regulated looping interactions; the location of YY1-mediated interactions may be demarcated in development by a pre-existing topological framework created by constitutive CTCF-mediated interactions. Overall design: Analysis of CTCF binding and higher-order chromatin architecture in mouse ES cells under 2i/LIF and serum/LIF conditions, and primary NPCs. ChIP-Seq libraries and Chromosome-Conformation-Capture-Carbon-Copy (5C) libraries.

REANALYSIS of: GSE68582

INSTRUMENT(S): Illumina NextSeq 500 (Mus musculus)

SUBMITTER: Jennifer E Phillips-Cremins  

PROVIDER: GSE85185 | GEO | 2017-05-22

SECONDARY ACCESSION(S): PRJNA336482

REPOSITORIES: GEO

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Publications

YY1 and CTCF orchestrate a 3D chromatin looping switch during early neural lineage commitment.

Beagan Jonathan A JA   Duong Michael T MT   Titus Katelyn R KR   Zhou Linda L   Cao Zhendong Z   Ma Jingjing J   Lachanski Caroline V CV   Gillis Daniel R DR   Phillips-Cremins Jennifer E JE  

Genome research 20170523 7


CTCF is an architectural protein with a critical role in connecting higher-order chromatin folding in pluripotent stem cells. Recent reports have suggested that CTCF binding is more dynamic during development than previously appreciated. Here, we set out to understand the extent to which shifts in genome-wide CTCF occupancy contribute to the 3D reconfiguration of fine-scale chromatin folding during early neural lineage commitment. Unexpectedly, we observe a sharp decrease in CTCF occupancy durin  ...[more]

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