The tumour suppressor brain tumour (Brat) regulates linker histone dBigH1 expression in the Drosophila female germline and the early embryo

Abstract

Linker histones H1 are essential chromatin components that exist as multiple developmentally regulated variants. In metazoans, specific H1s are expressed during germline development in a tightly regulated manner. However, the mechanisms governing their stage-dependent expression are poorly understood. Here, we address this question in Drosophila , which encodes for a single germline-specific dBigH1 linker histone. We show that during female germline lineage differentiation, dBigH1 is expressed in germ stem cells and cystoblasts, becomes silenced during transit-amplifying (TA) cystocytes divisions to resume expression after proliferation stops and differentiation starts, when it progressively accumulates in the oocyte. We find that dBigH1 silencing during TA divisions is post-transcriptional and depends on the tumour suppressor Brain tumour (Brat), an essential RNA-binding protein that regulates mRNA translation and stability. Like other oocyte-specific variants, dBigH1 is maternally expressed during early embryogenesis until it is replaced by somatic dH1 at the maternal-to-zygotic transition (MZT). Brat also mediates dBigH1 silencing at MZT. Finally, we discuss the situation in testes, where Brat is not expressed, but dBigH1 is translationally silenced too.

Chromatin Organization and Function in Drosophila

“…BigH1 is expressed in both male and female germlines with similar expression patterns [ 50 , 65 , 66 ]. While the function in the female germline is not known, in males, BigH1 is important for germ stem cell maintenance and spermatocyte differentiation [ 65 ].…”

“…BigH1 is retained in precellular embryos, where it is important in maintaining the silencing of the zygotic genome [ 50 ]. Recent studies have focused on the different properties of the two linker histones and have found that BigH1 has a greater repression ability than the somatic H1 due to its higher content in acidic residues [ 66 ]. Moreover, nucleosomes containing BigH1 are more stable, but show higher mobility than H1-nucleosomes [ 67 ].…”

A rapidly evolving single copy histone H1 variant is associated with male fertility in a parasitoid wasp

“…Germline-enriched histone H1 variants have been reported in many metazoan species, and studies on the model species of some key taxa have revealed that the germline-enriched H1 variants play crucial roles in gametogenesis ( Pérez-Montero et al, 2016 ). In insects, one of the most diverse groups of animals on Earth, the knowledge of germline-enriched H1 variants was limited to Drosophila species ( Carbonell et al, 2017 ; Climent-Cantó et al, 2021 ), and very little is known about these variants in other insects. In this study, we reported two testis-specific highly expressed H1 variant genes ( PpH1V1 and PpH1V2 ) in the parasitoid wasp P. puparum , and functional studies suggested that PpH1V1 is associated with male fertility in the wasp.…”

The Potential Reversible Transition between Stem Cells and Transient-Amplifying Cells: The Limbal Epithelial Stem Cell Perspective

“…Mediates polarity to ensure a robust pattern of asymmetric division [163] Tumor suppressor brain tumor (Brat) Regulates the linker histone dBigH1 expression [164] Niche-derived Hh and Wnts and germline-derived EGFs Promotes the differentiation of GSCs [165] Insulin/IGF signaling, TOR signaling, and GCN2-dependent amino acid sensing Promotes the proliferation and maintenance of the stem/progenitor population [161,162] Retinoic acid-STRA8 signaling…”