About

Professor Aaron Straight is the Chair of Biochemistry at Stanford University and serves as a Principal Investigator at the Stanford Straight Lab. The provided page text does not include specific details about his research focus, background, or key contributions. Therefore, no further biographical information is available from the given content.

Research topics

• Biology
• Computational biology
• Genetics
• Evolutionary biology

Selected publications

• Phosphorylation of Xenopus M18BP1 governs centromeric localization and CENP-A nucleosome assembly

  EMBO Reports · 2026-02-12

  articleOpen accessSenior authorCorresponding

  Eukaryotic chromosome segregation requires attachment of chromosomes to microtubules through the kinetochore so that chromosomes can align and move in mitosis. Kinetochores assemble on the centromere, which is epigenetically defined by the histone H3 variant CENtromere Protein A (CENP-A). During DNA replication, CENP-A is equally divided between replicated chromatids, and new CENP-A nucleosomes are re-assembled during the subsequent G1 phase. How cells regulate the cell cycle timing of CENP-A assembly is a central question in the epigenetic maintenance of centromeres. CENP-A nucleosome assembly requires the Mis18 complex (Mis18α, Mis18β, and M18BP1), whose localization to centromeres occurs between metaphase and G1. Here, we define a new regulatory mechanism that works through phosphorylation of Xenopus laevis M18BP1 between metaphase and interphase. Phosphorylation disrupts binding of M18BP1 to CENP-A nucleosomes in metaphase, and when relieved, enables M18BP1 binding to CENP-A nucleosomes in interphase. We show that this phosphorylation-dependent mechanism regulates CENP-A nucleosome assembly. We propose that the phospho-regulated binding of M18BP1 to CENP-A nucleosomes restricts new CENP-A assembly to interphase.

  PublisherOA PDFDOI

• Haplotype-resolved centromeric chromatin organization from a complete diploid human genome

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-31

  articleOpen access

  Centromeres ensure proper chromosome segregation during cell division, yet the organization and regulation of centromeric chromatin within satellite DNA arrays remain incompletely understood. Here, we leverage the complete diploid human genome benchmark (T2T-HG002) to provide a detailed study of centromeric sequence and chromatin architecture on individual haplotypes. Using adaptive-sampling-enriched, ultra-long-read DiMeLo-seq, we achieve single-molecule chromatin profiling across all centromeres, revealing that along single chromatin fibers, CENP-A, the histone variant specifying centromere identity, forms multiple discrete subdomains within hypomethylated centromere dip regions (CDRs) that are flanked by H3K9me3-enriched heterochromatin. Despite underlying sequence variation, CDRs localize to sequence-homogeneous domains and maintain relatively balanced CENP-A dosage and aggregate length across all chromosomes and between haplotypes. Further, we show that bidirectional changes to centromeric and pericentromeric DNA methylation are accompanied by changes to centromeric chromatin architecture. In passaged cells with centromeric hypomethylation, subdomain boundaries are eroded, and adjacent CENP-A domains tend to merge and expand. Conversely, in pluripotent stem cells with centromeric hypermethylation, CDRs are fundamentally reorganized, such that discrete hypomethylated domains are frequently consolidated into broader contiguous tracts. These methylation-associated CDR restructuring events suggest that DNA methylation acts as a principal regulator of human centromere organization, with implications for understanding centromere plasticity, epigenetic inheritance, and chromosomal instability in development and disease.

  PublisherDOI

• Identification of chromatin-associated RNAs at human centromeres

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-08 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Centromeres are a specialized chromatin domain that are required for the assembly of the mitotic kinetochore and the accurate segregation of chromosomes. Non-coding RNAs play essential roles in regulating genome organization including at the unique chromatin environment present at human centromeres. We performed Chromatin-Associated RNA sequencing (ChAR-seq) in three different human cell lines to identify and map RNAs associated with centromeric chromatin. Centromere enriched RNAs display distinct contact behaviors across repeat arrays and generally belong to three categories: centromere encoded, nucleolar localized, and highly abundant, broad-binding RNAs. Most centromere encoded RNAs remain locally associated with their transcription locus with the exception of a subset of human satellite RNAs. This work provides a comprehensive identification of centromere bound RNAs that may regulate the organization and activity of the centromere.

  PublisherOA PDFDOI

• Histone H3 lysine methyltransferase activities control compartmentalization of human centromeres

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-04 · 5 citations

  preprintOpen accessSenior authorCorresponding

  Centromeres are essential chromosomal regions that ensure accurate genome segregation during cell division. They are organized into epigenetically discrete compartments: a Centromere Protein A (CENP-A)-rich core for microtubule attachment and surrounding heterochromatic pericentromeres that promote cohesion. Despite their importance, the mechanisms that define, enforce and partition these chromatin domains remain poorly understood. To address this, we disrupted key H3K9 methyltransferases- SUV39H1, SUV39H2, and SETDB1- that establish heterochromatin in humans. We find that SETDB1 is required for H3K9 dimethylation at core centromeres, while SUV39H1/2 complete trimethylation. Unexpectedly, depleting all three enzymes results in aberrantly high H3K9me3, driving CENP-A expansion into pericentromeres. This promiscuous deposition is mediated by G9a/GLP methyltransferases, which selectively reestablish H3K9me3 within the centromere core. SETDB1, regardless of its enzymatic activity, blocks G9a/GLP-mediated heterochromatin deposition and CENP-A expansion, revealing a novel, catalytic-independent function in safeguarding centromeres. Overall, our work defines the molecular logic governing centromeric repression, and uncovers foundational principles of epigenetic compartmentalization.

  PublisherOA PDFDOI

• Purification and Activity Testing for Nanobody-Hia5 Fusions v1

  2025-06-17

  preprintOpen accessSenior author

  This protocol is for the purification of nanobody-Hia5 fusions for use in DiMeLo-seq experiments. It also includes an assay for MTase activity in a non-targeted context, useful for validating individual preparations. The purification consists of a duel affinity sequence of Ni-NTA followed by amylose binding, leveraging the constructs' 6X Histidine and maltose binding protein (MBP) tags. This protocol accompanies Sidhwani et al. (2025) “Histone H3 lysine methyltransferase activities control compartmentalization of human centromeres.” and Gamarra et al. (2025) "DiMeLo-cito: a one-tube protocol for mapping protein-DNA interactions reveals CTCF bookmarking in mitosis" (DOI: 10.1101/2025.03.11.642717).

  PublisherOA PDFDOI

• Independence of centromeric and pericentromeric chromatin stability on CCAN components

  Molecular Biology of the Cell · 2025-02-12 · 2 citations

  article

  The chromatin of the centromere provides the assembly site for the mitotic kinetochore that couples microtubule attachment and force production to chromosome movement in mitosis. The chromatin of the centromere is specified by nucleosomes containing the histone H3 variant, CENP-A. The constitutive centromeric-associated network (CCAN) and kinetochore are assembled on CENP-A chromatin to enable chromosome separation. CENP-A chromatin is surrounded by pericentromeric heterochromatin, which itself is bound by the sequence specific binding protein, CENP-B. We performed mechanical experiments on mitotic chromosomes while tracking CENP-A and CENP-B to observe the centromere's stiffness and the role of the CCAN. We degraded CENP-C and CENP-N containing auxin-inducible degrons, which we verified compromises the CCAN via observation of CENP-T loss. Chromosome stretching revealed that the CENP-A domain does not visibly stretch, even in the absence of CENP-C and/or CENP-N. Pericentromeric chromatin deforms upon force application, stretching ∼3-fold less than the entire chromosome. CENP-C and/or CENP-N loss has no impact on pericentromere stretching. Chromosome-disconnecting nuclease treatments showed no structural effects on CENP-A. Our experiments show that the core-centromeric chromatin is more resilient and likely mechanically disconnected from the underlying pericentromeric chromatin, while the pericentric chromatin is deformable yet stiffer than the chromosome arms.

  PublisherDOI

• Integrated analysis of multimodal long-read epigenetic assays

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-09

  preprintOpen access

  Long-read sequencing assays that detect base modifications are becoming increasingly important research tools for the study of epigenetic regulation, especially with the development of DiMeLo-seq and similar methods that deposit non-native base modifications to mark a range of epigenetic features such as protein-DNA interactions and chromatin accessibility. A main benefit of these methods is their inherent capacity for multimodality, enabling the encoding of multiple genomic signals onto single nucleic acid molecules. However, there are limited tools available for visualization and statistical analysis of this type of multimodal data. Here we introduce dimelo-toolkit, a python package built to enable flexible visualizations and easy integration into custom data processing workflows. We demonstrate the utility of dimelo-toolkit's preset visualizations of multiple base modifications in long-read single-molecule sequencing data with a novel extension of the DiMeLo-seq protocol that can capture three separate aspects of chromatin state on the same single reads: target protein binding, CpG methylation, and chromatin accessibility. We apply this multimodal method to simultaneously map chromatin accessibility, CpG methylation, and LMNB1 and CTCF binding patterns, respectively, in GM12878 cells. Additionally, we use dimelo-toolkit to investigate technical biases that arise when working with this type of multimodal data. This software tool will pave the way for developing well-optimized protocols and help unlock previously inaccessible biological insights.

  PublisherOA PDFDOI

• DiMeLo-cito: a one-tube protocol for mapping protein-DNA interactions reveals CTCF bookmarking in mitosis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-14 · 8 citations

  preprintOpen access

  Genome regulation relies on complex and dynamic interactions between DNA and proteins. Recently, powerful methods have emerged that leverage third-generation sequencing to map protein-DNA interactions genome-wide. For example, Directed Methylation with Long-read sequencing (DiMeLo-seq) enables mapping of protein-DNA interactions along long, single chromatin fibers, including in highly repetitive genomic regions. However, DiMeLo-seq involves lossy centrifugation-based wash steps that limit its applicability to many sample types. To address this, we developed DiMeLo-cito, a single-tube, wash-free protocol that maximizes the yield and quality of genomic DNA obtained for long-read sequencing. This protocol enables the interrogation of genome-wide protein binding with as few as 100,000 cells and without the requirement of a nuclear envelope, enabling confident measurement of protein-DNA interactions during mitosis. Using this protocol, we detected strong binding of CTCF to mitotic chromosomes in diploid human cells, in contrast with earlier studies in karyotypically unstable cancer cell lines, suggesting that CTCF "bookmarks" specific sites critical for maintaining genome architecture across cell divisions. By expanding the capabilities of DiMeLo-seq to a broader range of sample types, DiMeLo-cito can provide new insights into genome regulation and organization.

  PublisherDOI

• Regulation of <i>X. laevis</i> M18BP1 centromeric localization and CENP-A assembly

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-15 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Eukaryotic chromosome segregation requires attachment of chromosomes to microtubules of the mitotic spindle through the kinetochore so that chromosomes can align and move in mitosis. Kinetochores are assembled on the centromere which is a unique chromatin domain that is epigenetically defined by the histone H3 variant CENtromere Protein A (CENP-A). During DNA replication CENP-A is equally divided between replicated chromatids and new CENP-A nucleosomes are re-assembled during the subsequent G1 phase of the cell cycle. How cells regulate the strict cell cycle timing of CENP-A assembly is a central question in the epigenetic maintenance of centromeres and kinetochores. One essential assembly factor for CENP-A nucleosomes is the Mis18 complex (Mis18α, Mis18β, and M18BP1) which is regulated in its localization to centromeres between metaphase and G1 when CENP-A assembly occurs. Here, we define a new regulatory mechanism that works through cell cycle dependent phosphorylation of Xenopus laevis M18BP1 between metaphase and interphase. This phosphoregulatory switch disrupts binding of M18BP1 to CENP-A nucleosomes in metaphase, and when relieved enables M18BP1 binding to CENP-A nucleosomes in interphase. We show that this phosphorylation dependent switching mechanism regulates CENP-A nucleosome assembly. We propose that the phospho-regulated binding of M18BP1 to CENP-A nucleosomes is an important control mechanism that restricts the timing of new CENP-A assembly.

  PublisherOA PDFDOI

• Conserved chromatin and repetitive patterns reveal slow genome evolution in frogs

  Nature Communications · 2024-01-17 · 40 citations

  articleOpen access

  Frogs are an ecologically diverse and phylogenetically ancient group of anuran amphibians that include important vertebrate cell and developmental model systems, notably the genus Xenopus. Here we report a high-quality reference genome sequence for the western clawed frog, Xenopus tropicalis, along with draft chromosome-scale sequences of three distantly related emerging model frog species, Eleutherodactylus coqui, Engystomops pustulosus, and Hymenochirus boettgeri. Frog chromosomes have remained remarkably stable since the Mesozoic Era, with limited Robertsonian (i.e., arm-preserving) translocations and end-to-end fusions found among the smaller chromosomes. Conservation of synteny includes conservation of centromere locations, marked by centromeric tandem repeats associated with Cenp-a binding surrounded by pericentromeric LINE/L1 elements. This work explores the structure of chromosomes across frogs, using a dense meiotic linkage map for X. tropicalis and chromatin conformation capture (Hi-C) data for all species. Abundant satellite repeats occupy the unusually long (~20 megabase) terminal regions of each chromosome that coincide with high rates of recombination. Both embryonic and differentiated cells show reproducible associations of centromeric chromatin and of telomeres, reflecting a Rabl-like configuration. Our comparative analyses reveal 13 conserved ancestral anuran chromosomes from which contemporary frog genomes were constructed.

  PublisherOA PDFDOI

Recent grants

• Control and coordination of the maternal-to-zygotic transition

  NIH · $1.6M · 2016–2021

• Mechanisms of Kinetochore Assembly

  NIH · $6.6M · 2005–2027

• Genome wide identification and functional analysis of chromatin regulatory RNAs

  NIH · $1.9M · 2017–2022

• NIH Grant S10RR026775

  NIH · $465k · 2011

• NIH Grant R21HD073772

  NIH · $426k · 2015

Frequent coauthors

• Timothy J. Mitchison

  Center for Systems Biology

  26 shared

• James R. Sellers

  National Heart Lung and Blood Institute

  17 shared

• Owen K. Smith

  Stanford University

  15 shared

• Gary H. Karpen

  University of California, Berkeley

  13 shared

• Charles Limouse

  12 shared

• Aaron Streets

  University of California, Berkeley

  12 shared

• Colin J. Fuller

  11 shared

• Kousik Sundararajan

  Stanford University

  11 shared

Labs

• Straight LabPI

  Not provided

Education

• AB

  Dartmouth College

• Post-doctoral, Cell Biology

  Harvard Medical School

• Ph.D., Biochemistry

  University of California San Francisco

Awards & honors

• Elected into the American Academy of Arts & Sciences (2026)
• AAAS Fellow (2025)