Research group Group Ozata

As a new research group aiming to construct an international work environment with a mutual respect, our main objective is to enthusiastically investigate how a mammalian male germ cell commits to become a functional sperm. Our studies will therefore advance our understanding of sperm development and may suggest approaches to promote fertility.


Male infertility has increased over the last two decades seven percent of which retains unknown reasons, thereby causing negative social and psychological impact. Sperm development (spermatogenesis) comprises an intricate and exquisitely programmed process of stem cell self-renewal, meiosis, and final differentiation that generates haploid, mature swimming sperm. Particularly, meiosis involves extensive changes in gene expression program that is critical for constructing mature swimming sperm. Therefore, precise regulation of gene expression program ensures male fertility.

We recently uncovered the novel function of a testis-specific transcription factor, TCFL5, during sperm development. In fact, transcription factors A-MYB and TCFL5 establish a central regulatory circuit that ensures the stepwise progression of spermatogenesis. However, two-fifths of genes required for sperm development are not regulated by this circuit, and thus we are interested in examining functions of additional transcription factors regulating sperm development.

Importantly, A-MYB–TCFL5 axis regulates ~100 specialized genes that produce highly abundant small RNAs, pachytene PIWI-interacting RNAs (piRNAs) that guide PIWI proteins to cleave/silence target transcripts. Only two of the mouse pachytene piRNA genes have mutant phenotypes: mice lacking pi6 or pi18 genes—on chromosomes 6 and 8—produce defective sperm. More puzzling, the sequences of pachytene piRNA genes unprecedentedly diverge faster than nearly all other genomic sequences in mammals, even among human individuals. Hence, the biological function of pachytene piRNAs is not well understood. We are therefore interested in exploring the evolutionary function of pachytene piRNAs during mammalian sperm development.

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CRISPR-induced exon skipping of β-catenin - Journal of Pathology, 2023 Jan 15. Mou H, Eskiocak O, Özler K, Gorman M, Yue J, Jin Y, Wang Z, Wang Z, Gao Y, Janowitz T, Meyer HV, Yu T, Wilkinson JE, Kucukural A, Ozata DM†, Beyaz S†. (†correspondence author; contributed equally).

The testis-specific transcription factor TCFL5 responds to A-MYB to elaborate the male meiotic - program in mice. Reproduction. 2022 Nov 1;REP-22-0355. Cecchini K, Yu T, Biasini A, Mou H, Arif A, Colpan C, Gainetdinov I, de Rooij DG, Weng Z, Zamore PD†, Ozata DM†. (†correspondence author).

A-MYB/TCFL5 regulatory architecture ensures the production of pachytene piRNAs in placental mammals - RNA. 2022 Oct 14;rna.079472.122. Yu T, Biasini A, Cecchini K, Säflund M, Mou H, Arif A, Eghbali A, de Rooij D, Weng Z, Zamore PD†, Ozata DM†. (†Co-correspondence author).

GTSF1 accelerates target RNA cleavage by PIWI-clade Argonaute proteins - Nature, 2022 June 30. Arif A, Bailey S, Izumi N, Anzelon T, Ozata DM, Andersson C, Gainetdinov I, MacRea I, Tomari Y, Zamore PD.

Terminal Modification, Sequence, and Length Determine Small RNA Stability in Animals. - Molecular Cell. 2021 Dec2; 4826-4842.e8. Gainetdinov I, Colpan C, Cecchini K, Albosta P, Jouravleva K, Vega-Badillo J, Lee Y, Ozata DM, Zamore PD.

Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal - tumorigenesis. Cell Stem Cell. 2021 Nov4; 1922-1935.e5. 5. Beyaz S, Chung C, Mou H, Bauer-Rowe KE, Xifaras ME, Ergin I, Dohnalova L, Biton M, Shekhar K, Eskiocak O, Papciak K, Ozler K, Almeqdadi M, Yueh B, Fein M, Annamalai D, Valle-Encinas E, Erdemir A, Dogum K, Shah V, Alici-Garipcan A, V Meyer H, Ozata DM, Elinav E, Kucukural A, Kumar P, McAleer JP, Fox JG, Thaiss CA, Regev A, Roper J, Orkin SH, Yilmaz OH.

Long first exons and epigenetic marks distinguish conserved pachytene piRNA clusters from other - mammalian genes. Nature Communications. 2021 Jan4;12(1):73. Yu T, Kaili F, Ozata DM, Zhang G, Fu Y, Theurkauf W, Zamore PD, Weng Z.

An Evolutionarily Conserved piRNA-producing Locus Required for Male Mouse Fertility. - Nature Genetics. 2020 Jul;52(7):728-739. Wu PH, Fu Y, Cecchini K, Ozata DM, Arif A, Yu T, Colpan C, Gainetdinov I, Weng Z, Zamore PD.

Evolutionarily Conserved Pachytene piRNA Loci are Highly Divergent among Modern Humans. - Nature Ecology & Evolution. 2020 Jan;4(1):156-168. Ozata DM, Yu T, Mou H, Gainetdinov I, Colpan C, Cecchini K, Kaymaz Y, Wu PH, Kaili Fan, Kucukural A, Weng Z, Zamore PD.

Inhibiting YAP1 in hepatoblastoma drives therapeutic differentiation of tumor cells to functional - hepatocyte-like cells. Hepatology. 2020 May 26. 10. Smith J, Rodriguez T, Mou H, SY Kwan, Pratt H, Cao Y, Ozata DM, Liang S, Hazeltine M, Weng Z, Sontheimer E, Xue W.

Depletion of TRRAP induces p53-independent senescence in liver cancer by downregulating mitotic - genes. Hepatology. 2020 Jan;71(1):275-290. 11. Kwan SY, Sheel A, Song CQ, Zhang XO, Jiang T, Dang H, Cao Y, Ozata DM, Mou H, Yin H, Weng Z, Wang WX, Xue W.

CRISPR-SONIC: targeted somatic oncogene knock-in enables rapid in vivo cancer modeling. - Genome Medicine. 2019 Apr16;11(1):21. Mou H, Ozata DM, Smith JL+, Sheel A, Kwan SY, Hough S, Kucukural A, Kennedy Z, Cao Y, Xue W.

PIWI-interacting RNAs: small RNAs with big functions - Nature Reviews Genetics. 2019 Feb; 20(2):89-108. Ozata DM, Gainetdinov I, Zoch A, O’Carroll D, Zamore PD.

DEBrowser: Interactive differential expression analysis and visualization tool for count data. - BMC Genomics. 2019 Jan 5;20(1):6. Kucukural A, Yukselen O, Ozata DM, Moore MJ, Garber M.

CRISPR/Cas9-mediated genome editing induces exon skipping by alternative splicing or exon deletion. - Genome Biology. 2017. Jun 14;18(1):108. Mou H, Smith JL, Peng L, Yin H, Moore J, Zhang XO, Song CQ, Sheel A, Wu Q, Ozata DM, Li Y, Anderson DG, Emerson CP, Sontheimer EJ, Moore MJ, Weng Z, and Xue W.

Genetic disruption of oncogenic Kras sensitizes lung cancer cells to Fas receptor-mediated apoptosis - Proc Natl Acad Sci USA. 2017. Apr 4;114(14):3648-3653. Mou H, Moore J, Malonia S, Li Y, Ozata DM, Hough S, Song CQ, Smith JL, Fischer A, Weng Z, Green M, Xue W.

Loss of miR-514a-3p regulation of PEG3 activates the NF-kappa B pathway in human testicular germ - cell tumors. Cell Death & Disease. 2017 May 4;8(5):e2759. Ozata DM†, Li X, Lee L, Warsito D, Hajeri P, Hultman I, Fotouhi O, Marklund S, Ahrlund-Richter L, Juhlin CC, Larsson C, Lui WO†. (†Co-correspondence author).

MicroRNA expression patterns associated with hyperfunctioning and non-hyperfunctioning pehnotypes in - adrenocortical adenomas. European Journal of Endocrinology. 2014 Mar 8; 170(4):583-91. Fernandez DV, Caramuta S, Ozata DM, Lu M, Höög A, Bäckdahl M, Larsson C, Lui WO, Zedenius J.

Role of microRNAs and microRNA machinery in the pathogenesis of diffuse large B-cell lymphoma - Blood Cancer Journal. 2013. Oct 11;3:e152. 19. Caramuta S, Lee L, Ozata DM, Akcakaya P, Georgii-Hemming P, Xie H, Amini RM, Lawrie CH, Enblad G, Larsson C, Lui WO.

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Department of Molecular Biosciences, The Wenner-Gren Institute

Read SU's interview with Deniz Ozata

The article covers the Ozata group’s research and their aim of advancing the understanding of sperm development. Read the article in Swedish

Department of Molecular Biosciences, The Wenner-Gren Institute

Ozata group publishes in RNA Journal

A-MYB/TCFL5 regulatory architecture ensures the production of pachytene piRNAs in placental mammals

Department of Molecular Biosciences, The Wenner-Gren Institute

Ozata group publishes in Reproduction

The transcription factor TCFL5 responds to A-MYB to elaborate the male meiotic program in mice

Department of Molecular Biosciences, The Wenner-Gren Institute

The mystery of piRNA-guided endonuclease activity of PIWI is resolved

Argonaute super family proteins comprise AGO and PIWI clades that are generally guided by small RNAs to cleave target transcripts. Although AGO clade proteins are highly efficient to cleave target transcripts, Arif et al. demonstrated that PIWI proteins are sluggish in cleaving their targets, thereby requiring additional factor, GTSF1, which transforms PIWI proteins into efficient endoribonuclease. Arif and her colleagues’ findings provide the first example of an auxiliary protein potentiating the catalytic activity of Argonaute super family protein.

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