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AML displays increa...
AML displays increased CTCF occupancy associated with aberrant gene expression and transcription factor binding
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- Mujahed, Huthayfa (author)
- Ctr Hematol & Regenerat Med, Dept Med, Huddinge, Sweden.
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- Miliara, Sophia (author)
- Karolinska Institutet
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- Neddermeyer, Anne H. (author)
- Uppsala universitet,Hematologi
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- Bengtzen, Sofia (author)
- Ctr Hematol & Regenerat Med, Dept Med, Huddinge, Sweden.
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- Nilsson, Christer (author)
- Karolinska Institutet
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- Deneberg, Stefan (author)
- Karolinska Institutet
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- Cordeddu, Lina (author)
- Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
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- Ekwall, Karl (author)
- Karolinska Institutet
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- Lennartsson, Andreas (author)
- Karolinska Institutet
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- Lehmann, Sören (author)
- Karolinska Institutet,Uppsala universitet,Hematologi
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Karolinska Institutet Ctr Hematol & Regenerat Med, Dept Med, Huddinge, Sweden (creator_code:org_t)
- American Society of Hematology, 2020
- 2020
- English.
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 136:3, s. 339-352
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Subject headings
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- CCTC-binding factor (CTCF) is a key regulator of gene expression through organization of the chromatin structure. Still, it is unclear how CTCF binding is perturbed in leukemia or in cancer in general. We studied CTCF binding by chromatin immunoprecipitation sequencing in cells from patients with acute myeloid leukemia (AML) and in normal bone marrow (NBM) in the context of gene expression, DNA methylation, and azacitidine exposure. CTCF binding was increased in AML compared with NBM. Aberrant CTCF binding was enriched for motifs for key myeloid transcription factors such as CEBPA, PU.1, and RUNX1. AML with TET2 mutations was characterized by a particularly strong gain of CTCF binding, highly enriched for gain in promoter regions, while AML in general was enriched for changes at enhancers. There was a strong anticorrelation between CTCF binding and DNA methylation. Gain of CTCF occupancy was associated with increased gene expression; however, the genomic location (promoter vs distal regions) and enrichment of motifs (for repressing vs activating cofactors) were decisive for the gene expression pattern. Knockdown of CTCF in K562 cells caused loss of CTCF binding and transcriptional repression of genes with changed CTCF binding in AML, as well as loss of RUNX1 binding at RUNX1/CTCF-binding sites. In addition, CTCF knockdown caused increased differentiation. Azacitidine exposure caused major changes in CTCF occupancy in AML patient cells, partly by restoring a CTCF-binding pattern similar to NBM. We conclude that AML displays an aberrant increase in CTCF occupancy that targets key genes for AML development and impacts gene expression.
Subject headings
- NATURVETENSKAP -- Biologi -- Utvecklingsbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Developmental Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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Blood
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- By the author/editor
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Mujahed, Huthayf ...
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Miliara, Sophia
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Neddermeyer, Ann ...
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Bengtzen, Sofia
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Nilsson, Christe ...
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Deneberg, Stefan
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show more...
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Cordeddu, Lina
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Ekwall, Karl
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Lennartsson, And ...
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Lehmann, Sören
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Developmental Bi ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Blood
- By the university
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Uppsala University
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Karolinska Institutet