Browsing by Author "Davis, Eric S."

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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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    Temporal analysis suggests a reciprocal relationship between 3D chromatin structure and transcription
    (Elsevier, 2022) Reed, Kathleen S. M.; Davis, Eric S.; Bond, Marielle L.; Cabrera, Alan; Thulson, Eliza; Quiroga, Ivana Yoseli; Cassel, Shannon; Woolery, Kamisha T.; Hilton, Isaac; Won, Hyejung; Love, Michael I.; Phanstiel, Douglas H.
    To infer potential causal relationships between 3D chromatin structure, enhancers, and gene transcription, we mapped each feature in a genome-wide fashion across eight narrowly spaced time points of macrophage activation. Enhancers and genes connected by loops exhibit stronger correlations between histone H3K27 acetylation and expression than can be explained by genomic distance or physical proximity alone. At these looped enhancer-promoter pairs, changes in acetylation at distal enhancers precede changes in gene expression. Changes in gene expression exhibit a directional bias at differential loop anchors; gained loops are associated with increased expression of genes oriented away from the center of the loop, and lost loops are often accompanied by high levels of transcription within the loop boundaries themselves. These results are consistent with a reciprocal relationship where loops can facilitate increased transcription by connecting promoters to distal enhancers, whereas high levels of transcription can impede loop formation.