Biology subjects

Kataruka, S.

Publications and source records attributed to Kataruka, S..

4 recordsLinked to original sources

bioRxiv2026

Paternal regulation of H3K4 methylation supports tumor suppressor networks in mammals intergenerationally

Paternally-inherited epigenetic information can influence phenotype in offspring (1). Here, we identify a critical mechanistic contribution of KDM6A (UTX), an X-linked histone modifier and tumor suppressor, in regulating transmissible epigenetic information in mammalian sperm. Paternal loss of KDM6A increases cancer risk in genetically wild type offspring, but how Kdm6a knockout sperm transmit this effect at the molecular level is unknown (2). We find that KDM6A functions in spermatogenesis to promote methylation of histone H3 lysine 4 (H3K4) via selective interaction with the COMPASS complex methyltransferase KMT2C (MLL3). KMT2C and KDM6A are coordinately recruited to promoters of active genes in spermatogenic cells, contrasting with recruitment to intergenic enhancers in other cell types (3, 4). Loss of KDM6A disrupts H3K4 methylation at promoters of tumor suppressor genes in spermatogonia, and some of these defects persist in epididymal sperm and correspond to impaired expression in preimplantation embryos. These genes are also misregulated in normal and malignant hematopoietic tissue of genetically wild type offspring, indicating that impaired H3K4 methylation in KDM6A-deficient male germ cells may preferentially alter regulation of tumor suppressor gene networks in development across generations.

genetics↗

bioRxiv2024

ISWI chromatin remodeler SMARCA5 is essential for meiotic gene expression and male fertility in mammals

Regulation of the transcriptome to promote meiosis is important for sperm development and fertility. However, how chromatin remodeling directs the transcriptome during meiosis in male germ cells is largely unknown. Here, we demonstrate that the ISWI family ATP-dependent chromatin remodeling factor SMARCA5 (SNF2H) plays a critical role in regulating meiotic prophase progression during spermatogenesis. Males with germ cell-specific depletion of SMARCA5 are infertile and unable to form sperm. Loss of Smarca5 results in failure of meiotic progression with abnormal spermatocytes beginning at the pachytene stage and an aberrant global increase in chromatin accessibility, especially at genes important for meiotic prophase.

genetics↗

bioRxiv2021

Physiologically relevant miRNAs in mammalian oocytes are rare and highly abundant.

miRNAs, ~22nt small RNAs associated with Argonaute (AGO) proteins, are important negative regulators of gene expression in mammalian cells. However, mammalian maternal miRNAs show negligible repressive activity and the miRNA pathway is dispensable for oocytes and maternal-to-zygotic transition. The stoichiometric hypothesis proposed that this is caused by dilution of maternal miRNAs during oocyte growth. As the dilution affects miRNAs but not mRNAs, it creates unfavorable miRNA:mRNA stoichiometry for efficient repression of cognate mRNAs. Here we report that porcine ssc-miR-205 and bovine bta-miR-10b are exceptional miRNAs, which resist the diluting effect of oocyte growth and can efficiently suppress gene expression. Additional analysis of ssc-miR-205 shows that it has higher stability, reduces expression of endogenous targets, and contributes to porcine oocyte-to-embryo transition. Consistent with the stoichiometric hypothesis, our results show that the endogenous miRNA pathway in mammalian oocytes is intact and that maternal miRNAs can efficiently suppress gene expression when a favorable miRNA:mRNA stoichiometry is established.

molecular biology↗

bioRxiv2019

Low miRNA abundance disables microRNA pathway in mammalian oocytes

MicroRNAs (miRNAs) are ubiquitous small RNAs, which guide post-transcriptional gene repression in countless biological processes. However, the miRNA pathway in mouse oocytes appears inactive and is dispensable for development. We report that miRNAs do not accumulate like maternal mRNAs during oocyte growth. The most abundant miRNAs total tens of thousands of molecules in fully-grown oocytes, a number similar to that observed in much smaller fibroblasts. The lack of miRNA accumulation acts like miRNA knock-down, where miRNAs can engage their targets but are not abundant enough to produce significant silencing effect. Injection of 100,000 miRNAs was sufficient to restore reporter repression in oocytes, confirming that miRNA inactivity primarily stems from low miRNA abundance and not from an active repression of the miRNA pathway per se. Similar situation was observed in rat, hamster, porcine, and bovine oocytes arguing that miRNA inactivity is not a mouse-specific adaptation but a common mammalian oocyte feature.

molecular biology↗