RRC ID 72653
Author Yamamoto-Matsuda H, Miyoshi K, Moritoh M, Yoshitane H, Fukada Y, Saito K, Yamanaka S, Siomi MC.
Title Lint-O cooperates with L(3)mbt in target gene suppression to maintain homeostasis in fly ovary and brain.
Journal EMBO Rep
Abstract Loss-of-function mutations in Drosophila lethal(3)malignant brain tumor [l(3)mbt] cause ectopic expression of germline genes and brain tumors. Loss of L(3)mbt function in ovarian somatic cells (OSCs) aberrantly activates germ-specific piRNA amplification and leads to infertility. However, the underlying mechanism remains unclear. Here, ChIP-seq for L(3)mbt in cultured OSCs and RNA-seq before and after L(3)mbt depletion shows that L(3)mbt genomic binding is not necessarily linked to gene regulation and that L(3)mbt controls piRNA pathway genes in multiple ways. Lack of known L(3)mbt co-repressors, such as Lint-1, has little effect on the levels of piRNA amplifiers. Identification of L(3)mbt interactors in OSCs and subsequent analysis reveals CG2662 as a novel co-regulator of L(3)mbt, termed "L(3)mbt interactor in OSCs" (Lint-O). Most of the L(3)mbt-bound piRNA amplifier genes are also bound by Lint-O in a similar fashion. Loss of Lint-O impacts the levels of piRNA amplifiers, similar to the lack of L(3)mbt. The lint-O-deficient flies exhibit female sterility and tumorous brains. Thus, L(3)mbt and its novel co-suppressor Lint-O cooperate in suppressing target genes to maintain homeostasis in the ovary and brain.
Volume 23(10)
Pages e53813
Published 2022-10-6
DOI 10.15252/embr.202153813
PMID 35993198
PMC PMC9535798
MeSH Animals Brain / metabolism Brain Neoplasms* / metabolism Co-Repressor Proteins / metabolism Drosophila / genetics Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster / genetics Drosophila melanogaster / metabolism Female Homeostasis Ovary / metabolism RNA, Small Interfering / genetics
IF 7.497
Drosophila TBX-0002 TBX-0009