TINC— A Method to Dissect Regulatory Complexes at Single-Locus Resolution— Reveals an Extensive Protein Complex at the Nanog Promoter

Anja S. Knaupp, Monika Mohenska, Michael R. Larcombe, Ethan Ford, Sue Mei Lim, Kayla Wong, Joseph Chen, Jaber Firas, Cheng Huang, Xiaodong Liu, Trung Nguyen, Yu B.Y. Sun, Melissa L. Holmes, Pratibha Tripathi, Jahnvi Pflueger, Fernando J. Rossello, Jan Schröder, Kathryn C. Davidson, Christian M. Nefzger, Partha P. DasJody J. Haigh, Ryan Lister, Ralf B. Schittenhelm, Jose M. Polo

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Cellular identity is ultimately dictated by the interaction of transcription factors with regulatory elements (REs) to control gene expression. Advances in epigenome profiling techniques have significantly increased our understanding of cell-specific utilization of REs. However, it remains difficult to dissect the majority of factors that interact with these REs due to the lack of appropriate techniques. Therefore, we developed TINC: TALE-mediated isolation of nuclear chromatin. Using this new method, we interrogated the protein complex formed at the Nanog promoter in embryonic stem cells (ESCs) and identified many known and previously unknown interactors, including RCOR2. Further interrogation of the role of RCOR2 in ESCs revealed its involvement in the repression of lineage genes and the fine-tuning of pluripotency genes. Consequently, using the Nanog promoter as a paradigm, we demonstrated the power of TINC to provide insight into the molecular makeup of specific transcriptional complexes at individual REs as well as into cellular identity control in general.

Original languageEnglish
Pages (from-to)1246-1259
Number of pages14
JournalStem Cell Reports
Volume15
Issue number6
DOIs
Publication statusPublished - 8 Dec 2020

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