A bioinformatics screen reveals hox and chromatin remodeling factors at the Drosophila histone locus

Author:

Hodkinson Lauren J.,Smith Connor,Comstra H. Skye,Ajani Bukola A.,Albanese Eric H.,Arsalan Kawsar,Daisson Alvaro Perez,Forrest Katherine B.,Fox Elijah H.,Guerette Matthew R.,Khan Samia,Koenig Madeleine P.,Lam Shivani,Lewandowski Ava S.,Mahoney Lauren J.,Manai Nasserallah,Miglay JonCarlo,Miller Blake A.,Milloway Olivia,Ngo Nhi,Ngo Vu D.,Oey Nicole F.,Punjani Tanya A.,SiMa HaoMin,Zeng Hollis,Schmidt Casey A.,Rieder Leila E.

Abstract

Abstract Background Cells orchestrate histone biogenesis with strict temporal and quantitative control. To efficiently regulate histone biogenesis, the repetitive Drosophila melanogaster replication-dependent histone genes are arrayed and clustered at a single locus. Regulatory factors concentrate in a nuclear body known as the histone locus body (HLB), which forms around the locus. Historically, HLB factors are largely discovered by chance, and few are known to interact directly with DNA. It is therefore unclear how the histone genes are specifically targeted for unique and coordinated regulation. Results To expand the list of known HLB factors, we performed a candidate-based screen by mapping 30 publicly available ChIP datasets of 27 unique factors to the Drosophila histone gene array. We identified novel transcription factor candidates, including the Drosophila Hox proteins Ultrabithorax (Ubx), Abdominal-A (Abd-A), and Abdominal-B (Abd-B), suggesting a new pathway for these factors in influencing body plan morphogenesis. Additionally, we identified six other factors that target the histone gene array: JIL-1, hormone-like receptor 78 (Hr78), the long isoform of female sterile homeotic (1) (fs(1)h) as well as the general transcription factors TBP associated factor 1 (TAF-1), Transcription Factor IIB (TFIIB), and Transcription Factor IIF (TFIIF). Conclusions Our foundational screen provides several candidates for future studies into factors that may influence histone biogenesis. Further, our study emphasizes the powerful reservoir of publicly available datasets, which can be mined as a primary screening technique.

Funder

Office of Extramural Research, National Institutes of Health

Publisher

Springer Science and Business Media LLC

Subject

Health Informatics,Genetics

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