About

Grant Hartzog is a Professor of Molecular, Cell & Developmental Biology at UC Santa Cruz. He holds a B.A. from UC Berkeley, a Ph.D. from UC San Francisco, and completed postdoctoral work at Harvard Medical School. His research focuses on understanding the role of chromatin in gene expression and the mechanisms by which chromatin structure is manipulated to regulate transcription. He studies this in the yeast Saccharomyces cerevisiae using biochemistry and genetics, with particular attention to proteins such as Spt4 and Spt5 that form a complex and modulate transcription by interacting with chromatin. Hartzog's work has shown that the Spt4-Spt5 complex facilitates transcription by removing nucleosomal barriers and reassembling nucleosomes behind transcribing RNA polymerase II, thus both promoting efficient transcription elongation and suppressing inappropriate transcription. His research also explores the association of this complex with RNA polymerase II and its recruitment to transcribed regions of genes. Additionally, his studies have identified interactions with other proteins involved in transcription elongation and chromatin structure, such as the Paf1 complex, Spt6, FACT, and Chd1. His work suggests links between transcription elongation and pre-mRNA processing, including splicing, and has demonstrated that mutations in Spt5 can cause splicing defects. His research contributes to a detailed understanding of the molecular mechanisms governing gene expression regulation.

Research topics

• Genetics
• Evolutionary biology
• Biology

Selected publications

• Spt5’s Central KOW Domains and the Pol II Stalk Collaborate to Regulate Chromatin and 3’-End Processing

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-13

  articleOpen accessSenior authorCorresponding

  Abstract Spt5 is a universally conserved multidomain transcription elongation factor that acts as a component of all Pol II elongation complexes. Structural studies indicate that several of Spt5’s central KOW domains lie adjacent to the Pol II stalk, composed of subunits Rpb4 and Rpb7. However, their in vivo functions are unknown. Here we show that Spt5 and Rpb4/7 jointly modulate 3’-end formation and co-transcriptional chromatin integrity in Saccharomyces cerevisiae . We identify mutations in the SPT5 KOW2-3 domains and RPB7 that cause cryptic initiation of transcription and alter 3’-end formation of RNA transcripts. Molecular readthrough assays reveal allele-specific changes at both GAL10 and SNR13, consistent with impacts on CPF/CF- and NNS-dependent termination. Proteomic experiments with isolated KOW2-3 domain enrich factors from both pathways as well as chromatin regulators, overlapping known Rpb7 interactors. Together, these findings support a model in which Spt5 KOW2-3/Pol II stalk region acts as a recruitment platform that coordinates pre-mRNA processing and chromatin dynamics during elongation, revealing new roles for the central KOW domains of Spt5. Summary This work describes a cooperative in vivo function for Spt5’s central KOW domains and the Pol II stalk in Saccharomyces cerevisiae . Allele-specific genetics and reporter assays show cooperative effects of SPT5 and RPB4/7 on cryptic initiation and 3′-end formation; double-mutant analyses reveal synthetic interactions. RT-qPCR at GAL10 and SNR13 demonstrates regulation of both poly(A) and non-coding transcript termination. Spt5 KOW pull-down proteomics enrich poly(A) and non-coding termination factors, as well as chromatin regulators that overlap with known Rpb7 interactors. Together, the data support a model in which Spt5 and the Pol II stalk coordinate chromatin integrity and termination during elongation.

  PublisherOA PDFDOI

• Wolbachia-mediated reduction in the glutamate receptor mGluR promotes female promiscuity and bacterial spread

  Cell Reports · 2025-05-01 · 3 citations

  articleOpen access

  The molecular mechanisms by which parasites mediate host behavioral changes remain largely unexplored. Here, we examine Drosophila melanogaster infected with Wolbachia, a symbiont transmitted through the maternal germline, and find Wolbachia infection increases female receptivity to male courtship and hybrid mating. Wolbachia colonize regions of the brain that control sense perception and behavior. Quantitative global proteomics identify 177 differentially abundant proteins in infected female larval brains. Genetic alteration of the levels of three of these proteins in adults, the metabotropic glutamate receptor mGluR, the transcription factor TfAP-2, and the odorant binding protein Obp99b, each mimic the effect of Wolbachia on female receptivity. Furthermore, >700 Wolbachia proteins are detected in infected brains. Through abundance and molecular modeling analyses, we distinguish several Wolbachia-produced proteins as potential effectors. These results identify potential networks of host and Wolbachia proteins that modify behavior to promote mating success and aid the spread of Wolbachia.

  PublisherOA PDFDOI

• Distinct <i>Wolbachia</i> localization patterns in oocytes of diverse host species reveal multiple strategies of maternal transmission

  Genetics · 2023 · 10 citations

  • Biology
  • Genetics
  • Evolutionary biology

  A broad array of endosymbionts radiate through host populations via vertical transmission, yet much remains unknown concerning the cellular basis, diversity, and routes underlying this transmission strategy. Here, we address these issues, by examining the cellular distributions of Wolbachia strains that diverged up to 50 million years ago in the oocytes of 18 divergent Drosophila species. This analysis revealed 3 Wolbachia distribution patterns: (1) a tight clustering at the posterior pole plasm (the site of germline formation); (2) a concentration at the posterior pole plasm, but with a significant bacteria population distributed throughout the oocyte; and (3) a distribution throughout the oocyte, with none or very few located at the posterior pole plasm. Examination of this latter class indicates Wolbachia accesses the posterior pole plasm during the interval between late oogenesis and the blastoderm formation. We also find that 1 Wolbachia strain in this class concentrates in the posterior somatic follicle cells that encompass the pole plasm of the developing oocyte. In contrast, strains in which Wolbachia concentrate at the posterior pole plasm generally exhibit no or few Wolbachia in the follicle cells associated with the pole plasm. Taken together, these studies suggest that for some Drosophila species, Wolbachia invade the germline from neighboring somatic follicle cells. Phylogenomic analysis indicates that closely related Wolbachia strains tend to exhibit similar patterns of posterior localization, suggesting that specific localization strategies are a function of Wolbachia-associated factors. Previous studies revealed that endosymbionts rely on 1 of 2 distinct routes of vertical transmission: continuous maintenance in the germline (germline-to-germline) or a more circuitous route via the soma (germline-to-soma-to-germline). Here, we provide compelling evidence that Wolbachia strains infecting Drosophila species maintain the diverse arrays of cellular mechanisms necessary for both of these distinct transmission routes. This characteristic may account for its ability to infect and spread globally through a vast range of host insect species.

  PublisherOA PDFDOI

• Distinct <i>Wolbachia</i> localization patterns in oocytes of diverse host species reveal multiple strategies of maternal transmission

  bioRxiv (Cold Spring Harbor Laboratory) · 2022

  • Biology
  • Genetics
  • Evolutionary biology

  ABSTRACT A broad array of endosymbionts radiate through host populations via vertical transmission, yet much remains unknown concerning the cellular basis, diversity and routes underlying this transmission strategy. Here we address these issues, by examining the cellular distributions of Wolbachia strains that diverged up to 50 million years ago in the oocytes of 18 divergent Drosophila species. This analysis revealed three Wolbachia distribution patterns: 1) a tight clustering at the posterior pole plasm (the site of germline formation); 2) a concentration at the posterior pole plasm, but with a significant bacteria population distributed throughout the oocyte; 3) and a distribution throughout the oocyte, with none or very few located at the posterior pole plasm. Examination of this latter class indicates Wolbachia accesses the posterior pole plasm during the interval between late oogenesis and the blastoderm formation. We also find that one Wolbachia strain in this class concentrates in the posterior somatic follicle cells that encompass the pole plasm of the developing oocyte. In contrast, strains in which Wolbachia concentrate at the posterior pole plasm generally exhibit no or few Wolbachia in the follicle cells associated with the pole plasm. Taken together, these studies suggest that for some Drosophila species, Wolbachia invade the germline from neighboring somatic follicle cells. Phylogenomic analysis indicates that closely related Wolbachia strains tend to exhibit similar patterns of posterior localization, suggesting that specific localization strategies are a function of Wolbachia -associated factors. Previous studies revealed that endosymbionts rely on one of two distinct routes of vertical transmission: continuous maintenance in the germline (germline-to-germline) or a more circuitous route via the soma (germline-to-soma-to-germline). Here we provide compelling evidence that Wolbachia strains infecting Drosophila species maintain the diverse arrays of cellular mechanisms necessary for both of these distinct transmission routes. This characteristic may account for its ability to infect and spread globally through a vast range of host insect species.

  PublisherOA PDFDOI

• An inclusive Research Education Community (iREC): Impact of the SEA-PHAGES program on research outcomes and student learning

  Proceedings of the National Academy of Sciences · 2017-12-05 · 212 citations

  articleOpen access

  Engaging undergraduate students in scientific research promises substantial benefits, but it is not accessible to all students and is rarely implemented early in college education, when it will have the greatest impact. An inclusive Research Education Community (iREC) provides a centralized scientific and administrative infrastructure enabling engagement of large numbers of students at different types of institutions. The Science Education Alliance-Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) is an iREC that promotes engagement and continued involvement in science among beginning undergraduate students. The SEA-PHAGES students show strong gains correlated with persistence relative to those in traditional laboratory courses regardless of academic, ethnic, gender, and socioeconomic profiles. This persistent involvement in science is reflected in key measures, including project ownership, scientific community values, science identity, and scientific networking.

  PublisherOA PDFDOI

• Plasmid DNAs designed for expression in Micromonas CCMP1545 v1 (protocols.io.i9wch7e)

  2017-01-01

  article
  Publisher

• Plasmid DNAs designed for expression in Micromonas CCMP1545 v1

  2017-08-06

  preprintOpen access

  We have available several plasmids designed for expression of Cas9, guide RNA, chloramphenicol acetyl-transferase, GFP, and beta-lactamase in Micromonas CCMP1545. For protein expression we used the promotor and 3' end elements from the endogenous RPS9 gene, and codon optimized the coding region. For expression of guide RNAs we used the Micromonas U6 snRNA promoter. DNA is available by contacting M. Ares &lt;ares@ucsc.edu&gt;. We have constructed and sequence verified 9 plasmids which we would like to make available to others attempting to detect transformation of DNA into Micromonas. Using the CCMP1545genome as a source for the U6 promoter sequence, and for the promoter and 3' UTR sequences of ribosomal protein RPS9, we built the following plasmids: CRISPR/Cas9 plasmids for Micromonas 1. Mp U6 promoter driving Bae cassette for guide RNA expression inpUC13 2. Mp RPS9-Cas9SV40-RPS9 in pUC13 3. BothMp U6 promoter driving Bae cassette for guide RNA expression andMp RPS9-Cas9SV40-RPS9 in pUC13 These first three plasmids were anticipated to enable stable incorporation of transgenes at specific genomic locations. BaeI is a type IIS restriction enzyme that leaves noncompatible sticky ends. In the context of the gRNA cassette, a pair of 24 nt oligos designed to have the sticky ends compatible with BaeI cleaved plasmid are annealed and cloned into the plasmid, replacing the BaeI cassette while adding the 20 nt target complementary sequence of the desired guide RNA. Selectable/Detectable Marker genes 4. Mp RPS9-codon optimized GFPsv40-RPS9 in pUC13 5. Mp RPS9-codon optimized chloramphenicol acetyltransferase-RPS9 in pUC13 6. Mp RPS9-codon optimized beta-lactamase-RPS9 in pUC13 These three plasmids have the indicated coding regions codon optimized for Micromonas flanked by RPS9 promoter and 3' end sequences. In the case of GFP, a nuclear localization signal from SV40 has been added to the C-terminus. Plasmids for Agrobacterium-mediated gene transfer 7. Mp RPS9-codon optimized GFPsv40-RPS9 in pOSCAR 8. Mp RPS9-codon optimized chloramphenicol acetyltransferase-RPS9 in pOSCAR 9. Mp RPS9-codon optimized beta-lactamase-RPS9 in pOSCAR

  PublisherDOI

• The yeast transcription elongation factor Spt4/5 is a sequence‐specific RNA binding protein

  Protein Science · 2016-07-04 · 12 citations

  articleOpen access

  The heterodimeric transcription elongation factor Spt4/Spt5 (Spt4/5) tightly associates with RNAPII to regulate both transcriptional elongation and co-transcriptional pre-mRNA processing; however, the mechanisms by which Spt4/5 acts are poorly understood. Recent studies of the human and Drosophila Spt4/5 complexes indicate that they can bind nucleic acids in vitro. We demonstrate here that yeast Spt4/5 can bind in a sequence-specific manner to single stranded RNA containing AAN repeats. Furthermore, we show that the major protein determinants for RNA-binding are Spt4 together with the NGN domain of Spt5 and that the KOW domains are not required for RNA recognition. These findings attribute a new function to a domain of Spt4/5 that associates directly with RNAPII, making significant steps towards elucidating the mechanism behind transcriptional control by Spt4/5.

  PublisherOA PDFDOI

• Comparative Genomics of Cluster O Mycobacteriophages

  PLoS ONE · 2015-03-05 · 25 citations

  articleOpen access

  Mycobacteriophages--viruses of mycobacterial hosts--are genetically diverse but morphologically are all classified in the Caudovirales with double-stranded DNA and tails. We describe here a group of five closely related mycobacteriophages--Corndog, Catdawg, Dylan, Firecracker, and YungJamal--designated as Cluster O with long flexible tails but with unusual prolate capsids. Proteomic analysis of phage Corndog particles, Catdawg particles, and Corndog-infected cells confirms expression of half of the predicted gene products and indicates a non-canonical mechanism for translation of the Corndog tape measure protein. Bioinformatic analysis identifies 8-9 strongly predicted SigA promoters and all five Cluster O genomes contain more than 30 copies of a 17 bp repeat sequence with dyad symmetry located throughout the genomes. Comparison of the Cluster O phages provides insights into phage genome evolution including the processes of gene flux by horizontal genetic exchange.

  PublisherOA PDFDOI

• Structure of the KOW1-Linker1 domain of Transcription Elongation Factor Spt5

  2015-03-17

  paratext
  PublisherDOI

Recent grants

• NIH Grant R01GM060479

  NIH · $2.2M · 2011

Frequent coauthors

• Fred Winston

  Harvard University

  22 shared

• Hiroshi Handa

  Tokyo Medical University

  20 shared

• Takuro Wada

  20 shared

• Tiffani K. Quan

  University of California, Santa Cruz

  18 shared

• Stephen Buratowski

  Harvard University

  17 shared

• Anwarul Ferdous

  The University of Texas Southwestern Medical Center

  16 shared

• Keiichi Yano

  16 shared

• Satoru Sugimoto

  Kyoto Prefectural University of Medicine

  16 shared

Education

• PhD, Biochemistry and Biophysics

  University of California, San Francisco

  1992

• BA, Biophysics

  University of California Berkeley

  1984