Targeted Enhancer Activation by a Subunit of the Integrator Complex.
Mol Cell
; 71(1): 103-116.e7, 2018 07 05.
Article
em En
| MEDLINE
| ID: mdl-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Monócitos
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Diferenciação Celular
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Elementos Facilitadores Genéticos
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Células Progenitoras Mieloides
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Proteína 1 de Resposta de Crescimento Precoce
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Proteína 2 de Resposta de Crescimento Precoce
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article