Browsing by Author "Rowley, M. Jordan"

Now showing 1 - 3 of 3
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    Chromatin alternates between A and B compartments at kilobase scale for subgenic organization
    (Springer Nature, 2023) Harris, Hannah L.; Gu, Huiya; Olshansky, Moshe; Wang, Ailun; Farabella, Irene; Eliaz, Yossi; Kalluchi, Achyuth; Krishna, Akshay; Jacobs, Mozes; Cauer, Gesine; Pham, Melanie; Rao, Suhas S. P.; Dudchenko, Olga; Omer, Arina; Mohajeri, Kiana; Kim, Sungjae; Nichols, Michael H.; Davis, Eric S.; Gkountaroulis, Dimos; Udupa, Devika; Aiden, Aviva Presser; Corces, Victor G.; Phanstiel, Douglas H.; Noble, William Stafford; Nir, Guy; Di Pierro, Michele; Seo, Jeong-Sun; Talkowski, Michael E.; Aiden, Erez Lieberman; Rowley, M. Jordan; Center for Theoretical Biological Physics
    Nuclear compartments are prominent features of 3D chromatin organization, but sequencing depth limitations have impeded investigation at ultra fine-scale. CTCF loops are generally studied at a finer scale, but the impact of looping on proximal interactions remains enigmatic. Here, we critically examine nuclear compartments and CTCF loop-proximal interactions using a combination of in situ Hi-C at unparalleled depth, algorithm development, and biophysical modeling. Producing a large Hi-C map with 33 billion contacts in conjunction with an algorithm for performing principal component analysis on sparse, super massive matrices (POSSUMM), we resolve compartments to 500 bp. Our results demonstrate that essentially all active promoters and distal enhancers localize in the A compartment, even when flanking sequences do not. Furthermore, we find that the TSS and TTS of paused genes are often segregated into separate compartments. We then identify diffuse interactions that radiate from CTCF loop anchors, which correlate with strong enhancer-promoter interactions and proximal transcription. We also find that these diffuse interactions depend on CTCF’s RNA binding domains. In this work, we demonstrate features of fine-scale chromatin organization consistent with a revised model in which compartments are more precise than commonly thought while CTCF loops are more protracted.
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    Predicting A/B compartments from histone modifications using deep learning
    (Elsevier, 2024) Zheng, Suchen; Thakkar, Nitya; Harris, Hannah L.; Liu, Susanna; Zhang, Megan; Gerstein, Mark; Aiden, Erez Lieberman; Rowley, M. Jordan; Noble, William Stafford; Gürsoy, Gamze; Singh, Ritambhara
    The three-dimensional organization of genomes plays a crucial role in essential biological processes. The segregation of chromatin into A and B compartments highlights regions of activity and inactivity, providing a window into the genomic activities specific to each cell type. Yet, the steep costs associated with acquiring Hi-C data, necessary for studying this compartmentalization across various cell types, pose a significant barrier in studying cell type specific genome organization. To address this, we present a prediction tool called compartment prediction using recurrent neural networks (CoRNN), which predicts compartmentalization of 3D genome using histone modification enrichment. CoRNN demonstrates robust cross-cell-type prediction of A/B compartments with an average AuROC of 90.9%. Cell-type-specific predictions align well with known functional elements, with H3K27ac and H3K36me3 identified as highly predictive histone marks. We further investigate our mispredictions and found that they are located in regions with ambiguous compartmental status. Furthermore, our model’s generalizability is validated by predicting compartments in independent tissue samples, which underscores its broad applicability.
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    Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample
    (Elsevier, 2024) Sandoval-Velasco, Marcela; Dudchenko, Olga; Rodríguez, Juan Antonio; Pérez Estrada, Cynthia; Dehasque, Marianne; Fontsere, Claudia; Mak, Sarah S. T.; Khan, Ruqayya; Contessoto, Vinícius G.; Oliveira Junior, Antonio B.; Kalluchi, Achyuth; Zubillaga Herrera, Bernardo J.; Jeong, Jiyun; Roy, Renata P.; Christopher, Ishawnia; Weisz, David; Omer, Arina D.; Batra, Sanjit S.; Shamim, Muhammad S.; Durand, Neva C.; O’Connell, Brendan; Roca, Alfred L.; Plikus, Maksim V.; Kusliy, Mariya A.; Romanenko, Svetlana A.; Lemskaya, Natalya A.; Serdyukova, Natalya A.; Modina, Svetlana A.; Perelman, Polina L.; Kizilova, Elena A.; Baiborodin, Sergei I.; Rubtsov, Nikolai B.; Machol, Gur; Rath, Krisha; Mahajan, Ragini; Kaur, Parwinder; Gnirke, Andreas; Garcia-Treviño, Isabel; Coke, Rob; Flanagan, Joseph P.; Pletch, Kelcie; Ruiz-Herrera, Aurora; Plotnikov, Valerii; Pavlov, Innokentiy S.; Pavlova, Naryya I.; Protopopov, Albert V.; Di Pierro, Michele; Graphodatsky, Alexander S.; Lander, Eric S.; Rowley, M. Jordan; Wolynes, Peter G.; Onuchic, José N.; Dalén, Love; Marti-Renom, Marc A.; Gilbert, M. Thomas P.; Aiden, Erez Lieberman; Center for Theoretical Biological Physics
    Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (†Mammuthus primigenius) that died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding 28 chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, and inactive X chromosome (Xi) superdomains persist. The active and inactive genome compartments in mammoth skin more closely resemble Asian elephant skin than other elephant tissues. Our analyses uncover new biology. Differences in compartmentalization reveal genes whose transcription was potentially altered in mammoths vs. elephants. Mammoth Xi has a tetradic architecture, not bipartite like human and mouse. We hypothesize that, shortly after this mammoth’s death, the sample spontaneously freeze-dried in the Siberian cold, leading to a glass transition that preserved subfossils of ancient chromosomes at nanometer scale.