Targeted Enhancer Activation by a Subunit of the Integrator Complex.

Molecular Cell
Elisa BarbieriAlessandro Gardini

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.

Citations

Sep 19, 2019·Genes & Development·Deirdre C TatomerJeremy E Wilusz
Nov 8, 2019·Blood·Katie A FennellMark A Dawson
Feb 23, 2020·Cold Spring Harbor Symposia on Quantitative Biology·Deirdre C Tatomer, Jeremy E Wilusz
Jan 30, 2020·Frontiers in Cell and Developmental Biology·Preston R ArnoldXian C Li
Jan 22, 2021·Nucleic Acids Research·Aishwarya GurumurthyJörg Bungert
Feb 7, 2021·Molecular Cell·Moritz M Pfleiderer, Wojciech P Galej
Feb 2, 2021·Science Advances·Marco TrizzinoAlessandro Gardini
Dec 20, 2020·Current Opinion in Cell Biology·Nina KirsteinRamin Shiekhattar
May 14, 2021·Molecular Cancer Research : MCR·Shuichi KimparaLixin Rui
May 22, 2021·Cancer Research·Santanu AdhikaryChandrima Das

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.