Monomethylated H3K27 is more than just an intermediate.

We often talk about biological traits as if they’re written in our DNA, but some of them aren’t in our DNA at all—instead, they’re on it in the form of chemical tags on the histone proteins our genomic DNA is wrapped around. During development, each cell’s genome is indexed with these tags, which help determine whether a stretch of DNA should be actively transcribed or silent. In a new study published in GENETICS, Wang et al. investigated how the marks left by one of the most important players in this system are interpreted.

PRC2 is a complex of proteins that turns off genes by flagging histones around the genes with methyl groups. One at a time, PRC2 adds these groups to a specific lysine residue (K27) of histone H3 through a process called methylation. Specifically, trimethylation of H3K27 is required for silencing; if there are any fewer than three methyl groups, the gene won’t be turned off.

DNA silenced in this way is relatively rare, with trimethylated H3K27 only being found at around 100 sites in the genome. In contrast, genomic regions littered with mono- and dimethylated H3K27 are more common. Wang et al. wondered whether these mono- and dimethylated H3K27 were simply intermediates left behind by PRC2 or had their own purposes.

To test for function of H3K27 monomethylation, the group engineered a version of PRC2 that was adept at adding one methyl group but very inefficient at adding more. They found that, in a fruit fly cell line, this version of PRC2 led to increased expression of genes that PRC2 normally targets for silencing. However, this wasn’t enough to show that monomethylation has a specific function, since silencing is known to require trimethylation of H3K27.

The real insight came from comparing this result to what happened when they ran the same experiment using a version of PRC2 that’s inefficient at adding any number of methyl groups. Cells with this defective PRC2 had lower expression of PRC2-target genes than cells with the monomethylating PRC2 did, indicating that having a single methyl group on H3K27 may specifically increase gene expression above baseline.

This study adds to a growing collection of work on the importance of the number of methyl groups added to histones. Monomethylation on a different lysine residue (K9) of the histone H3 is associated with active genes, whereas di- or trimethylation usually indicates gene repression. If different numbers of methyl groups lead to multiple, distinct states, this could be exploited in drug design. Many cancers are associated with faulty gene regulation, so a targeted drug that precisely tuned the number of methyl groups on histones could help restore order by rewriting the genome’s index.

CITATION:

A Role for Monomethylation of Histone H3-K27 in Gene Activity in Drosophila
Liangjun Wang, Preeti Joshi, Ellen L. Miller, LeeAnn Higgins, Matthew Slattery and Jeffrey A. Simon
Genetics 2018 208: 1023–1036; https://doi.org/10.1534/genetics.117.300585
http://www.genetics.org/content/208/3/1023

, , ,

Nicole Haloupek is a freelance science writer and a recent graduate of UC Berkeley's molecular and cell biology PhD program.

View all posts by Nicole Haloupek »

Read more in

  • Thank you, GSA community!

    Thank you for being a member of the Genetics Society of America! As GSA’s current president, I am writing to tell you about Society projects and initiatives that we hope you will find useful in advancing your science and your career. Scientific research is a collaborative and exciting endeavor. Scientific societies like GSA exist to…

  • Collage of 2021 Rosalind Franklin Award recipients

    Where are they now? Rosalind Franklin Young Investigator Award recipients share updates on their research

    Rosalind Franklin Young Investigator Award applications are open–make sure you submit your application or nomination of a colleague by September 30, 2024.

  • University of Minnesota researchers map genome of the last living wild horse species

    The study, published in G3: Genes|Genomes|Genetics, is part of larger conservation efforts to save Przewalski’s horse.

  • Congratulations to the Spring 2024 DeLill Nasser Awardees!

    GSA is pleased to announce the recipients of the DeLill Nasser Award for Professional Development in Genetics for Spring 2024! Given twice a year to graduate students and postdoctoral researchers, DeLill Nasser Awards support attendance at meetings and laboratory courses. The award is named in honor of DeLill Nasser, a long-time GSA supporter and National Science Foundation…

  • Carolyn Damilola headshot

    Carolyn Damilola: an NFS Rising Scientist on a lifelong quest to learn more

    Carolyn Damilola is an NFS Rising Scientist from Nigeria doing respiratory system research and paving the way for scientists from underrepresented communities through mentorship.

  • Text over a blue background image: Apply for up to $2,000 for your project from the Starter Culture Microgrant Program.

    What does a good microgrant proposal look like?

    Members of the Microgrant Review Committee share their tips for a successful proposal.

  • A blurred image of a human face is shown against a dark background.

    The first piece of the facial recognition puzzle

    New research in GENETICS gives a first peek at the molecular pathway involved in recognizing faces.

  • New Senior Editor Amy MacQueen joins GENETICS

    A new senior editor is joining GENETICS in the Genome Integrity and Transmission section. We’re excited to welcome Amy MacQueen to the editorial team.

  • Close up of an adult zebrafish with blue and white stripes in an aquarium with red lighting.

    Block party on the zebrafish sex chromosome

    Research in G3 identifies a gene regulatory block of the zebrafish genome responsible for overseeing the maternal-to-zygotic-transition.

  • Lemna Minor, the common duckweed

    Unraveling the mysteries of duckweed: epigenetic insights from Spirodela polyrhiza

    Research published in G3 offers insight into the impact of DNA methylation on clonal propagation in asexually reproducing plants.

  • Luciano Marraffini headshot

    A microbiologist’s quest to understand CRISPR in bacterial self-defense

    2024 Genetics Society of America Medal recipient Luciano Marraffini determined how CRISPR-Cas systems destroy genetic targets with precision, paving the way for gene editing technology development.

  • Elaine Ostrander headshot

    Unlocking mysteries of trait and disease heritability in dogs

    2024 Edward Novitski Prize recipient Elaine Ostrander, a pioneer of the domestic dog model, discovered numerous genes affecting dog size, morphology, behavior, and disease susceptibility—many of which have relevance in humans.

  • NSF-funded BIO-LEAPS Grant to Support Culture Change in Genetics

    GSA and collaborators Personal Genetics Education & Dialogue and Reclaiming STEM Institute launch NSF-funded BIO-LEAPS project to support culture change in genetics 

    We are thrilled to announce that the Genetics Society of America (GSA) is collaborating with the Personal Genetics Education & Dialogue (PGED) based in the Department of Genetics at Harvard Medical School, and the Reclaiming STEM Institute (RSI) on a Leading Culture Change Through Professional Societies of Biology (BIO-LEAPS) grant from the U.S. National Science…

  • Daman Saluja: Navigating Science and Policy in India

    In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the GSA Early Care­er Scientist…

  • Deborah Andrew headshot

    A fly geneticist’s journey into discovering rules of organ development

    2024 George W. Beadle Award recipient Deborah Andrew discovered new genes and pathways in Drosophila salivary gland organogenesis. Now, her work can help optimize cell secretion in therapeutic applications and fight malaria.

  • Małgorzata Gazda's headshot

    Małgorzata Gazda: How receiving the DeLill Nasser Award helped her land her dream job

    Have you ever experienced an event that changes the course of your life, or in this case, your career? Małgorzata (Gosia) Gazda is Assistant Professor at the University of Montreal and in 2022, she received the DeLill Nasser Award for Professional Development in Genetics, which she used to attend and present at the 2022 Population,…

  • Hongyu Zhao joins GENETICS as new Senior Editor

    A new senior editor is joining GENETICS in the Statistical Genetics and Genomics section. We’re excited to welcome Hongyu Zhao to the editorial team.

  • Julio Molina Pineda at TAGC 2024

    GSA Member Julio Molina Pineda Receives DeLill Nasser Award, Shines at TAGC 2024 

    “At any career stage, the GSA membership is an amazing investment for any genetics professional!” Julio Molina Pineda is a PhD Candidate in Cell and Molecular Biology and a Research Assistant at the University of Arkansas, and a Doctoral Academy Fellow at the Lewis Lab. In 2023, Julio was awarded the DeLill Nasser Award for…

  • Ed Grell at his dissecting microscope using ether to anesthetize his flies.

    In Memoriam: Ellsworth Herman Grell (1932–2023), a pioneer of Drosophila genome engineering and annotation

    Ellsworth (Ed) Grell blessed the Drosophila community through three enduring legacies: as a pioneer of chromosome mechanics, as a primary organizer and synthesizer of genetic knowledge in Drosophila, and as a graceful mentor to those fortunate to have known him personally. Ed grew up in rural Nebraska, completed his undergraduate studies at Iowa State, and…

  • Congratulations to the #Fungal24 Poster Award winners!

    We are pleased to announce the recipients of the GSA Poster Awards for posters presented at the 32nd Fungal Genetics Conference! Undergraduate and graduate student members of GSA were eligible for the awards, and a hard-working team of judges made the determinations. Congratulations to all! Felicia Ebot Ojong, The University of Georgia My research is focused…

  • Poster presentation tips for TAGC 2024

    You’ve been selected to present a poster at The Allied Genetics Conference 2024 in March—you’ve celebrated, made plans to attend, now what? This is an exciting opportunity to showcase your research and engage with fellow members of the genetics community, so you want to make sure you’re prepared. We wanted to offer you some tips…

  • Maximize your TAGC 2024 experience 

    A guide to all that National Harbor & DC have to offer Are you joining us for The Allied Genetics Conference 2024 in March? Make the most of your #TAGC24 experience in National Harbor! We know the science will keep you busy, but you deserve to unwind and have some fun, so we’ve curated a…

  • Early Career Leadership Spotlight: Sarah Petrosky

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Sarah PetroskyMultimedia SubcommitteeUniversity of Pittsburgh Research Interest I am interested in understanding adaptation that has been happening recently in populations by dissecting the ways that genes underlying an adaptation…

  • TAGC 2024 Early Career Award Winners

    GSA is pleased to announce the winners of the early career awards presented at The Allied Genetics Conference 2024. These awards are specific to particular TAGC communities and recognize early career scientists’ outstanding work on their respective research organisms. The awardees will present their talks in keynote sessions at TAGC 2024.  Don’t miss the opportunity…

  • Preeminent geneticists recognized with revamped GSA Awards

    In 2022, GSA’s Board of Directors launched an audit to review the five major awards conferred by the Society. Today, we are thrilled to announce the recipients of the reimagined GSA Awards, including the new Genetics Society of America Early Career Medal. The scientists honored this year are recognized by their peers for their outstanding…

  • Fly Board funds outreach programs to spread the word about Drosophila research

    In 2020, the Fly Board voted to use part of its reserve fund to support efforts to increase trainee participation as well as equity and diversity in the Drosophila community. An awards committee decides how the money will be spent each year, and from 2020–2022, the committee posted a very broad call for applications from…

  • New members of the GSA Board of Directors: 2024–2026

    We are pleased to announce the election of four new leaders to the GSA Board of Directors: 2024 Vice President/2025 President Brenda Andrews Professor, University of Toronto It’s an honor to continue my association with the Society by serving as Vice President of the Board of Directors. I have broad knowledge of the ongoing activities…

  • New members of the GSA Board of Directors: 2025–2027

    We are pleased to announce the election of six new leaders to the GSA Board of Directors: 2025 Vice President/2026 President Cassandra Extavour Timken Professor of Organismic & Evolutionary Biology and of Molecular & Cellular Biology, Harvard University, and Howard Hughes Medical Institute Investigator “Read this,” he said, “it will change your life.” My undergraduate…

  • Congratulations, Spring 2025 Victoria Finnerty Travel Award recipients!

    The Victoria Finnerty Undergraduate Travel Award supports conference-attendance costs for undergraduate GSA members who are presenting research at the Annual Drosophila Research Conference. #Dros25 will be held in San Diego, CA from March 19–23, 2025. Victoria Finnerty, who died in February 2011, was a long-time member of the Genetics Society of America and served the Drosophila community and the genetics community at large in…

  • Meet embGAN, a revolution for cell lineage studies

    New research in GENETICS reports an automated pipeline for cell lineage tracing that massively reduces manual analysis time.