Interplay Between BALL and CREB Binding Protein Maintains H3K27 Acetylation on Active Genes in Drosophila.

Ammad Shaukat,Muhammad Tariq,Muhammad Haider Farooq Khan,Zain Umer,Hina Ahmad

doi:10.3389/fcell.2021.740866

Ammad Shaukat, Muhammad Tariq + Show 3 more

Open Access

https://doi.org/10.3389/fcell.2021.740866

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Abstract

CREB binding protein (CBP) is a multifunctional transcriptional co-activator that interacts with a variety of transcription factors and acts as a histone acetyltransferase. In Drosophila, CBP mediated acetylation of histone H3 lysine 27 (H3K27ac) is a known hallmark of gene activation regulated by trithorax group proteins (trxG). Recently, we have shown that a histone kinase Ballchen (BALL) substantially co-localizes with H3K27ac at trxG target loci and is required to maintain gene activation in Drosophila. Here, we report a previously unknown interaction between BALL and CBP, which positively regulates H3K27ac. Analysis of genome-wide binding profile of BALL and CBP reveals major overlap and their co-localization at actively transcribed genes. We show that BALL biochemically interacts with CBP and depletion of BALL results in drastic reduction in H3K27ac. Together, these results demonstrate a previously unknown synergy between BALL and CBP and reveals a potentially new pathway required to maintain gene activation during development.

Highlights

In metazoans, covalent modifications of histones act in a combinatorial manner to regulate developmental gene expression (Allis and Jenuwein, 2016; Zhao and Shilatifard, 2019)
We have discovered that BALL binds to chromatin enriched with H3K27ac and shares more than 77% genomic binding sites with CREB binding protein (CBP)
We reported that BALL exhibits trithorax group (trxG) like behavior by contributing to the maintenance of gene activation in flies (Khan et al, 2021)

Summary

Introduction

Covalent modifications of histones act in a combinatorial manner to regulate developmental gene expression (Allis and Jenuwein, 2016; Zhao and Shilatifard, 2019). Chromatin immunoprecipitation sequencing (ChIP-seq) data from previously published reports revealed the presence of CBP on a majority BALL and CBP Maintain H3K27ac of actively transcribed genes in Drosophila S2 cells (Philip et al, 2015).

Results

Conclusion