Bap170, a Subunit of the Drosophila PBAP Chromatin Remodeling Complex, Negatively Regulates the EGFR Signaling

Abstract

BAP and PBAP constitute the two different forms of the Drosophila melanogaster Brahma chromatin remodelers. A common multisubunit core, containing the Brahma ATPase, can associate either with Osa to form the BAP complex or with Bap170, Bap180, and Sayp to constitute the PBAP complex. Although required for many biological processes, recent genetic analyses revealed that one role of the BAP complex during Drosophila wing development is the proper regulation of EGFR target genes. Here, we show that Bap170, a distinctive subunit of the PBAP complex, participates instead in the negative regulation of EGFR signaling. In adults, loss of Bap170 generates phenotypes similar to the defects induced by hyperactivation of the EGFR pathway, such as overrecruitment of cone and photoreceptor cells and formation extra veins. In genetic interactions, bap170 mutations suppress the loss of veins and photoreceptors caused by mutations affecting the activity of the EGFR pathway. Our results suggest a dual requirement of the PBAP complex: for transcriptional repression of rhomboid and for efficient expression of argos. Interestingly, genetic evidence also indicates that Bap170-mediated repression of rho is inhibited by EGFR signaling, suggesting a scenario of mutual antagonism between EGFR signaling and PBAP function.

The Many Roles of BAF (mSWI/SNF) and PBAF Complexes in Cancer

“…For example, PBAP but not BAP is required for germinal stem cell maintenance (He et al 2014). Moreover, BAP and PBAP have opposing roles in Egfr expression in wing development: whereas BAP positively regulates Egfr expression (Molnar et al 2006; Terriente-Felix and de Celis 2009), PBAP instead negatively regulates Egfr (Rendina et al 2010). Together, these observations suggest that mutations in different subunits or complexes may result in distinct or even opposing changes to the genomic landscape, a fact that complicates straightforward predictions of their effects.…”

PBAP chromatin remodeler mediates enhancer-driven transcription inDrosophila

“…This construct was used to obtain 20 independent transgenic lines, which were examined for the genomic insertion sites and orientations of the constructs. Driver transgenes for expression of LexA:SAYP or LexA:BAP170 were prepared using either the ubiquitous alpha-tubulin promoter (Ptub) or the less potent BAP170 promoter (PBAP170) to simulate nearly physiological levels of both subunits ( Fig 1B) [16]. As a control, a transgene was constructed to ensure ubiquitous expression of the LexA repressor under the Ptub promoter ( Fig 1B).…”

“…A common core complex includes Brahma (BRM, SMARCA2/4 in human and STH1/SNF2 in yeast), Moira (MOR, SMARCC1/2 in human and SWI3/RSC8 in yeast), and Snr1 (SMARCB1 in human and SNF5/ SFH1 in yeast) and can associate with the distinctive subunit OSA (ARID1A/B in human and SWI1 in yeast) to form the BAP complex or, alternatively, with Polybromo (PB, PBRM1 in human and RSC1/2/4 in yeast), BAP170 (ARID2 in human and RSC9 in yeast), and SAYP (PHF10 in human, no homolog in yeast) to produce the PBAP form [11,12]. Analysis of mutations affecting the signature subunits has demonstrated that BAP and PBAP execute distinct and partly antagonistic functions in transcription control and development with BAP being mainly involved in cell cycle regulation and PBAP, in signal transduction cascades and differentiation [12][13][14][15][16][17]. Interestingly, the PBAP subunits have a hierarchical role in the stability of the complex.…”

The Elongin Complex Antagonizes the Chromatin Factor Corto for Vein versus Intervein Cell Identity in Drosophila Wings

“…Several TrxG complexes are involved in control of vein vs intervein fate. Indeed, BAP and PBAP chromatin remodeling complexes participate in differential regulation of rho expression [20], [24], [25]. Furthermore, the Chromodomain Helicase DNA-binding protein encoded by the TrxG gene kismet ( kis ) [26], [27] also plays a role in vein development [28].…”