Institute of Molecular Biology of Barcelona, CSIC, Barcelona 08028, Spain.
Institute for Research in Biomedicine, IRB Barcelona, The Barcelona Institute for Science and Technology, Barcelona 08028, Spain.
Open Biol. 2021 May;11(5):200408. doi: 10.1098/rsob.200408. Epub 2021 May 5.
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 , 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.
连接组蛋白 H1 是必不可少的染色质成分，存在多种发育调控变体。在后生动物中，特定的 H1 在生殖系发育过程中以严格调控的方式表达。然而，其发育阶段表达的调控机制尚不清楚。在这里，我们在 中解决了这个问题，该基因编码一种单一的生殖系特异性 dBigH1 连接组蛋白。我们表明，在雌性生殖系谱系分化过程中，dBigH1 在生殖干细胞和囊胚母细胞中表达，在过渡扩增（TA）囊胚母细胞分裂期间沉默，在增殖停止和分化开始后重新表达，此时它逐渐积累在卵母细胞中。我们发现 TA 分裂期间的 dBigH1 沉默是转录后依赖的，并依赖于肿瘤抑制因子 Brain tumour (Brat)，这是一种必需的 RNA 结合蛋白，可调节 mRNA 翻译和稳定性。像其他卵母细胞特异性变体一样，dBigH1 在早期胚胎发生期间母系表达，直到在母源到合子过渡 (MZT) 时被体细胞 dH1 取代。Brat 也介导 MZT 时 dBigH1 的沉默。最后，我们讨论了在睾丸中的情况，其中 Brat 不表达，但 dBigH1 也被翻译沉默。
