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)

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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).

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Conclusion

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