Epigenomic mapping reveals distinct B cell acute lymphoblastic leukemia chromatin architectures and regulators

Kelly R. Barnett; Robert J. Mobley; Jonathan D. Diedrich; Brennan P. Bergeron; Kashi Raj Bhattarai; Alexander C. Monovich; Shilpa Narina; Wenjian Yang; Kristine R. Crews; Christopher S. Manring; Elias Jabbour; Elisabeth Paietta; Mark R. Litzow; Steven M. Kornblau; Wendy Stock; Hiroto Inaba; Sima Jeha; Ching Hon Pui; Charles G. Mullighan; Mary V. Relling; Shondra M. Pruett-Miller; Russell J.H. Ryan; Jun J. Yang; William E. Evans; Daniel Savic

doi:10.1016/j.xgen.2023.100442

Epigenomic mapping reveals distinct B cell acute lymphoblastic leukemia chromatin architectures and regulators

Kelly R. Barnett, Robert J. Mobley, Jonathan D. Diedrich, Brennan P. Bergeron, Kashi Raj Bhattarai, Alexander C. Monovich, Shilpa Narina, Wenjian Yang, Kristine R. Crews, Christopher S. Manring, Elias Jabbour, Elisabeth Paietta, Mark R. Litzow, Steven M. Kornblau, Wendy Stock, Hiroto Inaba, Sima Jeha, Ching Hon Pui, Charles G. Mullighan, Mary V. RellingShondra M. Pruett-Miller, Russell J.H. Ryan, Jun J. Yang, William E. Evans, Daniel Savic

Hematology

Research output: Contribution to journal › Article › peer-review

Abstract

B cell lineage acute lymphoblastic leukemia (B-ALL) is composed of diverse molecular subtypes, and while transcriptional and DNA methylation profiling has been extensively examined, the chromatin landscape is not well characterized for many subtypes. We therefore mapped chromatin accessibility using ATAC-seq in primary B-ALL cells from 156 patients spanning ten molecular subtypes and present this dataset as a resource. Differential chromatin accessibility and transcription factor (TF) footprint profiling were employed and identified B-ALL cell of origin, TF-target gene interactions enriched in B-ALL, and key TFs associated with accessible chromatin sites preferentially active in B-ALL. We further identified over 20% of accessible chromatin sites exhibiting strong subtype enrichment and candidate TFs that maintain subtype-specific chromatin architectures. Over 9,000 genetic variants were uncovered, contributing to variability in chromatin accessibility among patient samples. Our data suggest that distinct chromatin architectures are driven by diverse TFs and inherited genetic variants that promote unique gene-regulatory networks.

Original language	English (US)
Article number	100442
Journal	Cell Genomics
Volume	3
Issue number	12
DOIs	https://doi.org/10.1016/j.xgen.2023.100442
State	Published - Dec 13 2023

Keywords

ATAC-QTLs
ATAC-seq
acute lymphoblastic leukemia
chromatin accessibility
gene regulation
gene-regulatory network
genetic variation
transcription factor
transcription factor footprints

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology (miscellaneous)
Genetics

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10.1016/j.xgen.2023.100442

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Barnett, K. R., Mobley, R. J., Diedrich, J. D., Bergeron, B. P., Bhattarai, K. R., Monovich, A. C., Narina, S., Yang, W., Crews, K. R., Manring, C. S., Jabbour, E., Paietta, E., Litzow, M. R., Kornblau, S. M., Stock, W., Inaba, H., Jeha, S., Pui, C. H., Mullighan, C. G., ... Savic, D. (2023). Epigenomic mapping reveals distinct B cell acute lymphoblastic leukemia chromatin architectures and regulators. Cell Genomics, 3(12), Article 100442. https://doi.org/10.1016/j.xgen.2023.100442

Barnett, KR, Mobley, RJ, Diedrich, JD, Bergeron, BP, Bhattarai, KR, Monovich, AC, Narina, S, Yang, W, Crews, KR, Manring, CS, Jabbour, E, Paietta, E, Litzow, MR, Kornblau, SM, Stock, W, Inaba, H, Jeha, S, Pui, CH, Mullighan, CG, Relling, MV, Pruett-Miller, SM, Ryan, RJH, Yang, JJ, Evans, WE & Savic, D 2023, 'Epigenomic mapping reveals distinct B cell acute lymphoblastic leukemia chromatin architectures and regulators', Cell Genomics, vol. 3, no. 12, 100442. https://doi.org/10.1016/j.xgen.2023.100442

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title = "Epigenomic mapping reveals distinct B cell acute lymphoblastic leukemia chromatin architectures and regulators",

abstract = "B cell lineage acute lymphoblastic leukemia (B-ALL) is composed of diverse molecular subtypes, and while transcriptional and DNA methylation profiling has been extensively examined, the chromatin landscape is not well characterized for many subtypes. We therefore mapped chromatin accessibility using ATAC-seq in primary B-ALL cells from 156 patients spanning ten molecular subtypes and present this dataset as a resource. Differential chromatin accessibility and transcription factor (TF) footprint profiling were employed and identified B-ALL cell of origin, TF-target gene interactions enriched in B-ALL, and key TFs associated with accessible chromatin sites preferentially active in B-ALL. We further identified over 20% of accessible chromatin sites exhibiting strong subtype enrichment and candidate TFs that maintain subtype-specific chromatin architectures. Over 9,000 genetic variants were uncovered, contributing to variability in chromatin accessibility among patient samples. Our data suggest that distinct chromatin architectures are driven by diverse TFs and inherited genetic variants that promote unique gene-regulatory networks.",

keywords = "ATAC-QTLs, ATAC-seq, acute lymphoblastic leukemia, chromatin accessibility, gene regulation, gene-regulatory network, genetic variation, transcription factor, transcription factor footprints",

author = "Barnett, {Kelly R.} and Mobley, {Robert J.} and Diedrich, {Jonathan D.} and Bergeron, {Brennan P.} and Bhattarai, {Kashi Raj} and Monovich, {Alexander C.} and Shilpa Narina and Wenjian Yang and Crews, {Kristine R.} and Manring, {Christopher S.} and Elias Jabbour and Elisabeth Paietta and Litzow, {Mark R.} and Kornblau, {Steven M.} and Wendy Stock and Hiroto Inaba and Sima Jeha and Pui, {Ching Hon} and Mullighan, {Charles G.} and Relling, {Mary V.} and Pruett-Miller, {Shondra M.} and Ryan, {Russell J.H.} and Yang, {Jun J.} and Evans, {William E.} and Daniel Savic",

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doi = "10.1016/j.xgen.2023.100442",

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AU - Barnett, Kelly R.

AU - Mobley, Robert J.

AU - Diedrich, Jonathan D.

AU - Bergeron, Brennan P.

AU - Bhattarai, Kashi Raj

AU - Monovich, Alexander C.

AU - Narina, Shilpa

AU - Yang, Wenjian

AU - Crews, Kristine R.

AU - Manring, Christopher S.

AU - Jabbour, Elias

AU - Paietta, Elisabeth

AU - Litzow, Mark R.

AU - Kornblau, Steven M.

AU - Stock, Wendy

AU - Inaba, Hiroto

AU - Jeha, Sima

AU - Pui, Ching Hon

AU - Mullighan, Charles G.

AU - Relling, Mary V.

AU - Pruett-Miller, Shondra M.

AU - Ryan, Russell J.H.

AU - Yang, Jun J.

AU - Evans, William E.

AU - Savic, Daniel

PY - 2023/12/13

Y1 - 2023/12/13

N2 - B cell lineage acute lymphoblastic leukemia (B-ALL) is composed of diverse molecular subtypes, and while transcriptional and DNA methylation profiling has been extensively examined, the chromatin landscape is not well characterized for many subtypes. We therefore mapped chromatin accessibility using ATAC-seq in primary B-ALL cells from 156 patients spanning ten molecular subtypes and present this dataset as a resource. Differential chromatin accessibility and transcription factor (TF) footprint profiling were employed and identified B-ALL cell of origin, TF-target gene interactions enriched in B-ALL, and key TFs associated with accessible chromatin sites preferentially active in B-ALL. We further identified over 20% of accessible chromatin sites exhibiting strong subtype enrichment and candidate TFs that maintain subtype-specific chromatin architectures. Over 9,000 genetic variants were uncovered, contributing to variability in chromatin accessibility among patient samples. Our data suggest that distinct chromatin architectures are driven by diverse TFs and inherited genetic variants that promote unique gene-regulatory networks.

AB - B cell lineage acute lymphoblastic leukemia (B-ALL) is composed of diverse molecular subtypes, and while transcriptional and DNA methylation profiling has been extensively examined, the chromatin landscape is not well characterized for many subtypes. We therefore mapped chromatin accessibility using ATAC-seq in primary B-ALL cells from 156 patients spanning ten molecular subtypes and present this dataset as a resource. Differential chromatin accessibility and transcription factor (TF) footprint profiling were employed and identified B-ALL cell of origin, TF-target gene interactions enriched in B-ALL, and key TFs associated with accessible chromatin sites preferentially active in B-ALL. We further identified over 20% of accessible chromatin sites exhibiting strong subtype enrichment and candidate TFs that maintain subtype-specific chromatin architectures. Over 9,000 genetic variants were uncovered, contributing to variability in chromatin accessibility among patient samples. Our data suggest that distinct chromatin architectures are driven by diverse TFs and inherited genetic variants that promote unique gene-regulatory networks.

KW - ATAC-QTLs

KW - ATAC-seq

KW - acute lymphoblastic leukemia

KW - chromatin accessibility

KW - gene regulation

KW - gene-regulatory network

KW - genetic variation

KW - transcription factor

KW - transcription factor footprints

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JO - Cell Genomics

JF - Cell Genomics

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ER -

Epigenomic mapping reveals distinct B cell acute lymphoblastic leukemia chromatin architectures and regulators

Abstract

Keywords

ASJC Scopus subject areas

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