The same domain of Su(Hw) is required for enhancer blocking and direct promoter repression

Larisa Melnikova,Varvara Molodina,Anton Golovnin,Pavel Elizar’Ev,Pavel Georgiev,Margarita Kostyuchenko,Darya Chetverina,Maksim Erokhin

doi:10.1038/s41598-019-41761-6

Larisa Melnikova, Varvara Molodina + Show 6 more

Open Access

https://doi.org/10.1038/s41598-019-41761-6

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Abstract

Suppressor of Hairy-wing [Su(Hw)] is a DNA-binding architectural protein that participates in the organization of insulators and repression of promoters in Drosophila. This protein contains acidic regions at both ends and a central cluster of 12 zinc finger domains, some of which are involved in the specific recognition of the binding site. One of the well-described in vivo function of Su(Hw) is the repression of transcription of neuronal genes in oocytes. Here, we have found that the same Su(Hw) C-terminal region (aa 720–892) is required for insulation as well as for promoter repression. The best characterized partners of Su(Hw), CP190 and Mod(mdg4)-67.2, are not involved in the repression of neuronal genes. Taken together, these results suggest that an unknown protein or protein complex binds to the C-terminal region of Su(Hw) and is responsible for the direct repression activity of Su(Hw).

Highlights

High-resolution chromosome conformation capture techniques have provided evidence that regulatory elements form loops that are essential for gene regulation in higher eukaryotes[1,2,3,4,5,6]
We found that the same C-terminal region in Su(Hw) is required for enhancer blocking and for promoter repression
To further characterize Su(Hw) domains involved in repression, we selected five representative neural genes whose promoters are bound by Su(Hw) alone (Rph, cg32017, and Hs3st-A), by Su(Hw) and CP190 (Syn2), or by Su(Hw), CP190, and Mod(mdg4)-67.2 (Fig. 1a)

Summary

Introduction

High-resolution chromosome conformation capture techniques have provided evidence that regulatory elements form loops that are essential for gene regulation in higher eukaryotes[1,2,3,4,5,6]. The Su(Hw) protein contains the N-terminal region involved in the interaction with CP190, an array of 12 C2H2-type zinc finger domains, and the C-terminal region (aa 716–892) responsible for enhancer blocking activity[28,29,30,31,32]. The Mod(mdg4)-67.2 protein contains the N-terminal BTB/POZ domain and glutamine-rich (Q-rich) region which is common to all isoforms and the unique C-terminal region that is required for interaction with the 716–892 aa region of Su(Hw)[28,31,34]. The functions of Mod(mdg4)-67.2 are as yet unknown, except for its participation in recruiting the Su(Hw) complex to specific chromatin sites and masking the repression activity of Su(Hw)[31,41,42]. Strong co-localization of HIPP1 and Su(Hw) sites suggests that these proteins are in the same complex[33]

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Conclusion