The Dm-Myb Oncoprotein Contributes to Insulator Function and Stabilizes Repressive H3K27me3 PcG Domains

Juan F Santana; Mrutyunjaya Parida; Abby Long; Joshua Wankum; Anthony J Lilienthal; Krishna M Nukala; J. Robert Manak

doi:10.1016/j.celrep.2020.02.053

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The Dm-Myb Oncoprotein Contributes to Insulator Function and Stabilizes Repressive H3K27me3 PcG Domains

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The Dm-Myb Oncoprotein Contributes to Insulator Function and Stabilizes Repressive H3K27me3 PcG Domains

Juan F Santana, Mrutyunjaya Parida, Abby Long, Joshua Wankum, Anthony J Lilienthal, Krishna M Nukala and J. Robert Manak

Cell reports (Cambridge), Vol.30(10), pp.3218-3228.e5

03/10/2020

DOI: 10.1016/j.celrep.2020.02.053

PMCID: PMC7172335

PMID: 32160531

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Abstract

Drosophila Myb (Dm-Myb) encodes a protein that plays a key role in regulation of mitotic phase genes. Here, we further refine its role in the context of a developing tissue as a potentiator of gene expression required for proper RNA polymerase II (RNA Pol II) function and efficient H3K4 methylation at promoters. In contrast to its role in gene activation, Myb is also required for repression of many genes, although no specific mechanism for this role has been proposed. We now reveal a critical role for Myb in contributing to insulator function, in part by promoting binding of insulator proteins BEAF-32 and CP190 and stabilizing H3K27me3 Polycomb-group (PcG) domains. In the absence of Myb, H3K27me3 is markedly reduced throughout the genome, leading to H3K4me3 spreading and gene derepression. Finally, Myb is enriched at boundaries that demarcate chromatin environments, including chromatin loop anchors. These results reveal functions of Myb that extend beyond transcriptional regulation. [Display omitted] •Myb transcriptional potentiation optimizes H3K4 methylation and RNA Pol II function•Myb contributes to insulator function and promotes binding of BEAF-32 and CP190•Myb is required to stabilize H3K27me3 domains genome wide•Myb is enriched at TAD boundaries and chromatin loop anchors Myb has been considered a transcriptional activator of primarily M phase genes. Here, Santana et al. show that Myb also contributes to insulator function, in part by promoting binding of insulator factors, and is required to stabilize repressive domains in the genome.

BEAF-32

chromatin loop anchors

chromatin structure

CP190

CTCF

gene expression

H3K27me3

Myb

TAD

topologically associating domain

Details

Title: Subtitle: The Dm-Myb Oncoprotein Contributes to Insulator Function and Stabilizes Repressive H3K27me3 PcG Domains
Creators: Juan F Santana - Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242, USA
Mrutyunjaya Parida - Interdisciplinary Graduate Program in Informatics, University of Iowa, Iowa City, IA 52242, USA
Abby Long - Department of Biology, University of Iowa, Iowa City, IA 52242, USA
Joshua Wankum - Department of Biology, University of Iowa, Iowa City, IA 52242, USA
Anthony J Lilienthal - Department of Biology, University of Iowa, Iowa City, IA 52242, USA
Krishna M Nukala - Department of Biology, University of Iowa, Iowa City, IA 52242, USA
J. Robert Manak - Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.30(10), pp.3218-3228.e5
DOI: 10.1016/j.celrep.2020.02.053
PMID: 32160531
PMCID: PMC7172335
NLM abbreviation: Cell Rep
ISSN: 2211-1247
eISSN: 2211-1247
Publisher: Elsevier Inc
Grant note: name: National Institutes of Health Predoctoral Training Grant, award: T32GM008629; DOI: 10.13039/100008893, name: University of Iowa
Language: English
Date published: 03/10/2020
Academic Unit: Stead Family Department of Pediatrics; Pathology; Biology; Craniofacial Anomalies Research Center; Biochemistry and Molecular Biology
Record Identifier: 9984217422002771

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