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Targeted Enhancer Activation by a Subunit of the Integrator Complex

Targeted Enhancer Activation by a Subunit of the Integrator Complex

Elisa Barbieri, Marco Trizzino, Sarah Ann Welsh, Tori Alexandra Owens, Bruno Calabretta, Martin Carroll, Kavitha Sarma, Alessandro Gardini

Mol Cell. 2018 Jul 5;71(1):103-116.e7.

PMID: 30008316

Abstract:

The control of cell fate is an epigenetic process initiated by transcription factors (TFs) that recognize DNA motifs and recruit activator complexes and transcriptional machineries to chromatin. Lineage specificity is thought to be provided solely by TF-motif pairing, while the recruited activators are passive. Here, we show that INTS13, a subunit of the Integrator complex, operates as monocytic/macrophagic differentiation factor. Integrator is a general activator of transcription at coding genes and is required for eRNA maturation. Here, we show that INTS13 functions as an independent sub-module and targets enhancers through Early Growth Response (EGR1/2) TFs and their co-factor NAB2. INTS13 binds poised monocytic enhancers eliciting chromatin looping and activation. Independent depletion of INTS13, EGR1, or NAB2 impairs monocytic differentiation of cell lines and primary human progenitors. Our data demonstrate that Integrator is not functionally homogeneous and has TF-specific regulatory potential, revealing a new enhancer regulatory axis that controls myeloid differentiation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1504588004	NAB2		1504588-00-4	Price

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