Epigenetic Chromatin Regulation

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Small RNA-mediated transcriptional gene silencing is a fundamental process that has been observed in many different eukaryotes including fungi, plants, flies, worms and mammals. One of its main tasks is to neutralize the activity of transposable elements (TEs), which otherwise destabilize our genome and potentially cause diseases. Small RNAs use their base complementarities to TEs to specifically silence them. However, how cells ensure TE-silencing without disturbing expressions of normal genes is not fully understood.

The ciliated protozoan Tetrahymena identifies TE-derived sequences by a germline-some genome comparison mechanism using small RNAs during programmed DNA elimination, which provides fascinating examples of epigenetic genome regulations and important insights into the interaction between TEs and host genomes. Because programmed DNA elimination can be synchronously induced in laboratory in a large scale, it serves as a useful laboratory model for genetically and biochemically investigating small RNA-mediated chromatin regulation.

Using this tiny-hairy eukaryotic model, we aim to understand: how cells accumulate small RNAs specifically from TE-related sequences; how cells use those small RNAs to identify TE-related sequences; and how a small RNA pathway establishes silent chromatin environment (heterochromatin) on TE-related sequences.

Tetrahymena thermophila. Tetrahymena is a unicellular eukaryote. Tetrahymena has many cilia on its cell surface (green = anti-alpha tubulin staining). Tetrahymena has two different nuclei (stained purple), the smaller germline micronucleus (MIC) and the larger somatic macronucleus (MAC).

Kazufumi MOCHIZUKI
Researcher
0434359918

Kohei NAGAO
Researcher
0434359918

Tomoko NOTO
Ingénieur biologiste
ITA
0434359918

Julie SAKSOUK
ITA
0434359918

Publications of the team

Genome organization: Raison d'être of ancestral linkage groups.

Published the 05/06/2024 - Curr Biol , 34(11):R544-R546 38834029

Nagao K, Mochizuki K

A SUMO E3 ligase promotes long non-coding RNA transcription to regulate small RNA-directed DNA elimination.

Published the 10/01/2024 - Elife , 13 38197489

Shehzada S, Noto T, Saksouk J, Mochizuki K

Programmed DNA elimination: New metazoan models.

Published the 07/12/2022 - Curr Biol , 32(23):R1316-R1318 36473443

Mochizuki K

PIWI-Directed DNA Elimination for Tetrahymena Genetics.

Published the 08/07/2022 - Methods Mol Biol , 2509:53-68 35796956

Shehzada S, Mochizuki K

Arrested crossover precursor structures form stable homologous bonds in a Tetrahymena meiotic mutant.

Published the 17/02/2022 - PLoS One , 17(2):e0263691 35171923

Tian M, Mochizuki K, Loidl J

Genomes: Programmed DNA Elimination in a Parasitic Nematode.

Published the 09/09/2020 - Curr Biol , 30(17):R994-R996 32898499

Mochizuki K

Non-coding RNA Transcription in Tetrahymena Meiotic Nuclei Requires Dedicated Mediator Complex-Associated Proteins.

Published the 10/07/2019 - Curr Biol , 29(14):2359-2370.e5 31280995

Tian M, Mochizuki K, Loidl J

Diversification of small RNA amplification mechanisms for targeting transposon-related sequences in ciliates.

Published the 01/07/2019 - Proc Natl Acad Sci USA 31262823

Mutazono M, Noto T, Mochizuki K.

Small RNA-Mediated trans-Nuclear and trans-Element Communications in Tetrahymena DNA Elimination.

Published the 12/06/2018 - Curr Biol 29887308

Noto T, Mochizuki K

Whats, hows and whys of programmed DNA elimination in Tetrahymena.

Published the 13/10/2017 - Open Biol , 7(10) 29021213

Noto T, Mochizuki K

A Zip3-like protein plays a role in crossover formation in the SC-less meiosis of the protist Tetrahymena.

Published the 20/01/2017 - Mol Biol Cell , 28(6):825-833 28100637

Shodhan A, Kataoka K, Mochizuki K, Novatchkova M, Loidl J

Negative Regulators of an RNAi-Heterochromatin Positive Feedback Loop Safeguard Somatic Genome Integrity in Tetrahymena

Published the 01/01/2017 - Cell Rep. , 18(10):2494-2507 28273462

Suhren JH, Noto T, Kataoka K, Gao S, Liu Y, Mochizuki K.

Heterochromatin aggregation during DNA elimination in Tetrahymena is facilitated by a prion-like protein.

Published the 03/12/2016 - J Cell Sci , 130(2):480-489 27909245

Kataoka K, Mochizuki K

Structure of the germline genome of Tetrahymena thermophila and relationship to the massively rearranged somatic genome.

Published the 29/11/2016 - Elife , 5 27892853

Hamilton EP, Kapusta A, Huvos PE, Bidwell SL, Zafar N, Tang H, Hadjithomas M, Krishnakumar V, Badger JH, Caler EV, Russ C, Zeng Q, Fan L, Levin JZ, Shea T, Young SK, Hegarty R, Daza R, Gujja S, Wortman JR, Birren BW, Nusbaum C, Thomas J, Carey CM, Pritham EJ, Feschotte C, Noto T, Mochizuki K, Papazyan R, Taverna SD, Dear PH, Cassidy-Hanley DM, Xiong J, Miao W, Orias E, Coyne RS

Phosphorylation of an HP1-like protein is a prerequisite for heterochromatin body formation in Tetrahymena DNA elimination.

Published the 29/07/2016 - Proc Natl Acad Sci U S A , 113(32):9027-32 27466409

Kataoka K, Noto T, Mochizuki K

Phosphorylation of an HP1-like Protein Regulates Heterochromatin Body Assembly for DNA Elimination.

Published the 22/12/2015 - Dev Cell , 35(6):775-88 26688337

Kataoka K, Mochizuki K

Targeted Gene Disruption by Ectopic Induction of DNA Elimination in Tetrahymena.

Published the 25/07/2015 - Genetics , 201(1):55-64 26205990

Hayashi A, Mochizuki K

Small-RNA-Mediated Genome-wide trans-Recognition Network in Tetrahymena DNA Elimination.

Published the 23/06/2015 - Mol Cell , 59(2):229-42 26095658

Noto T, Kataoka K, Suhren JH, Hayashi A, Woolcock KJ, Gorovsky MA, Mochizuki K

A Tetrahymena Hsp90 co-chaperone promotes siRNA loading by ATP-dependent and ATP-independent mechanisms.

Published the 16/01/2015 - EMBO J , 34(4):559-77 25588944

Woehrer SL, Aronica L, Suhren JH, Busch CJ, Noto T, Mochizuki K

The taming of the shrew: Regulation of a catalytically active domesticated transposase.

Published the 24/07/2014 - Mob Genet Elements , 4:e29383 25054083

Vogt A, Mochizuki K

A domesticated PiggyBac transposase interacts with heterochromatin and catalyzes reproducible DNA elimination in Tetrahymena.

Published the 19/12/2013 - PLoS Genet , 9(12):e1004032 24348275

Vogt A, Mochizuki K

Epigenetics of ciliates.

Published the 04/12/2013 - Cold Spring Harb Perspect Biol , 5(12):a017764 24296171

Chalker DL, Meyer E, Mochizuki K

Analysis of Piwi-loaded small RNAs in Tetrahymena.

Published the 02/11/2013 - Methods Mol Biol , 1093:209-24 24178568

Noto T, Kurth HM, Mochizuki K

Transposon domestication versus mutualism in ciliate genome rearrangements.

Published the 13/08/2013 - PLoS Genet , 9(8):e1003659 23935529

Vogt A, Goldman AD, Mochizuki K, Landweber LF

Biased transcription and selective degradation of small RNAs shape the pattern of DNA elimination in Tetrahymena.

Published the 03/08/2012 - Genes Dev , 26(15):1729-42 22855833

Schoeberl UE, Kurth HM, Noto T, Mochizuki K

Developmentally programmed, RNA-directed genome rearrangement in Tetrahymena.

Published the 23/11/2011 - Dev Growth Differ , 54(1):108-19 22103557

Mochizuki K

DNA rearrangements directed by non-coding RNAs in ciliates.

Published the 01/10/2011 - Wiley Interdiscip Rev RNA , 1(3):376-87 21956937

Mochizuki K

Programmed DNA elimination in Tetrahymena: a small RNA-mediated genome surveillance mechanism.

Published the 15/09/2011 - Adv Exp Med Biol , 722:156-73 21915788

Kataoka K, Mochizuki K

Keeping the soma free of transposons: programmed DNA elimination in ciliates.

Published the 15/09/2011 - J Biol Chem , 286(43):37045-52 21914793

Schoeberl UE, Mochizuki K

RNA-directed epigenetic regulation of DNA rearrangements.

Published the 09/09/2010 - Essays Biochem , 48(1):89-100 20822488

Mochizuki K

Modules for C-terminal epitope tagging of Tetrahymena genes.

Published the 14/07/2010 - J Microbiol Methods , 82(3):342-6 20624430

Kataoka K, Schoeberl UE, Mochizuki K

MRE11 and COM1/SAE2 are required for double-strand break repair and efficient chromosome pairing during meiosis of the protist Tetrahymena.

Published the 28/04/2010 - Chromosoma , 119(5):505-18 20422424

Lukaszewicz A, Howard-Till RA, Novatchkova M, Mochizuki K, Loidl J

A domesticated piggyBac transposase plays key roles in heterochromatin dynamics and DNA cleavage during programmed DNA deletion in Tetrahymena thermophila.

Published the 02/04/2010 - Mol Biol Cell , 21(10):1753-62 20357003

Cheng CY, Vogt A, Mochizuki K, Yao MC

The Tetrahymena argonaute-binding protein Giw1p directs a mature argonaute-siRNA complex to the nucleus.

Published the 10/03/2010 - Cell , 140(5):692-703 20211138

Noto T, Kurth HM, Kataoka K, Aronica L, DeSouza LV, Siu KW, Pearlman RE, Gorovsky MA, Mochizuki K

Two GW repeat proteins interact with Tetrahymena thermophila argonaute and promote genome rearrangement.

Published the 15/07/2009 - Mol Cell Biol , 29(18):5020-30 19596782

Bednenko J, Noto T, DeSouza LV, Siu KW, Pearlman RE, Mochizuki K, Gorovsky MA

Non-coding RNA: a bridge between small RNA and DNA.

Published the 12/03/2009 - RNA Biol , 6(2):138-40 19276654

Kurth HM, Mochizuki K

2'-O-methylation stabilizes Piwi-associated small RNAs and ensures DNA elimination in Tetrahymena.

Published the 26/02/2009 - RNA , 15(4):675-85 19240163

Kurth HM, Mochizuki K

High efficiency transformation of Tetrahymena using a codon-optimized neomycin resistance gene.

Published the 09/09/2008 - Gene , 425(1-2):79-83 18775482

Mochizuki K

Study of an RNA helicase implicates small RNA-noncoding RNA interactions in programmed DNA elimination in Tetrahymena.

Published the 19/08/2008 - Genes Dev , 22(16):2228-41 18708581

Aronica L, Bednenko J, Noto T, DeSouza LV, Siu KW, Loidl J, Pearlman RE, Gorovsky MA, Mochizuki K

DNA double-strand breaks, but not crossovers, are required for the reorganization of meiotic nuclei in Tetrahymena.

Published the 05/06/2008 - J Cell Sci , 121(Pt 13):2148-58 18522989

Mochizuki K, Novatchkova M, Loidl J

A Dicer-like protein in Tetrahymena has distinct functions in genome rearrangement, chromosome segregation, and meiotic prophase.

Published the 16/12/2004 - Genes Dev , 19(1):77-89 15598983

Mochizuki K, Gorovsky MA

RNA polymerase II localizes in Tetrahymena thermophila meiotic micronuclei when micronuclear transcription associated with genome rearrangement occurs.

Published the 08/10/2004 - Eukaryot Cell , 3(5):1233-40 15470252

Mochizuki K, Gorovsky MA

Conjugation-specific small RNAs in Tetrahymena have predicted properties of scan (scn) RNAs involved in genome rearrangement.

Published the 18/08/2004 - Genes Dev , 18(17):2068-73 15314029

Mochizuki K, Gorovsky MA

Histone H3 lysine 9 methylation is required for DNA elimination in developing macronuclei in Tetrahymena.

Published the 03/02/2004 - Proc Natl Acad Sci U S A , 101(6):1679-84 14755052

Liu Y, Mochizuki K, Gorovsky MA

Analysis of a piwi-related gene implicates small RNAs in genome rearrangement in tetrahymena.

Published the 26/09/2002 - Cell , 110(6):689-99 12297043

Mochizuki K, Fine NA, Fujisawa T, Gorovsky MA

Universal occurrence of the vasa-related genes among metazoans and their germline expression in Hydra.

Published the 24/07/2001 - Dev Genes Evol , 211(6):299-308 11466525

Mochizuki K, Nishimiya-Fujisawa C, Fujisawa T

Expression and evolutionary conservation of nanos-related genes in Hydra.

Published the 11/01/2001 - Dev Genes Evol , 210(12):591-602 11151296

Mochizuki K, Sano H, Kobayashi S, Nishimiya-Fujisawa C, Fujisawa T

Thèses et hdr

Regulations of small RNA turnover during programmed DNA removal in Tetrahymena 28/10/2022

Defended by Salman Shehzada on october 28th 2022 under the direction of Kazufumi Mochizuki

Characterisation of proteins required for RNA-mediated heterochromatin formation 04/12/2020

Defended by Elliot Geraud the 04/12/2020

Epigenetic Chromatin Regulation

Publications of the team

Thèses et hdr

Regulations of small RNA turnover during programmed DNA removal in Tetrahymena 28/10/2022

Characterisation of proteins required for RNA-mediated heterochromatin formation 04/12/2020

Head : Kazufumi MOCHIZUKI

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