Schuetzmann, Daniel and Walter, Carolin and van Riel, Boet and Kruse, Sabrina and Koenig, Thorsten and Erdmann, Tabea and Toenges, Alexander and Bindels, Eric and Weilemann, Andre and Gebhard, Claudia and Wethmar, Klaus and Perrod, Chiara and Minderjahn, Julia and Rehli, Michael and Delwel, Ruud and Lenz, Georg and Groeschel, Stefan and Dugas, Martin and Rosenbauer, Frank (2018) Temporal autoregulation during human PU.1 locus SubTAD formation. BLOOD, 132 (25). pp. 2643-2655. ISSN 0006-4971, 1528-0020
Full text not available from this repository. (Request a copy)Abstract
Epigenetic control of gene expression occurs within discrete spatial chromosomal units called topologically associating domains (TADs), but the exact spatial requirements of most genes are unknown; this is of particular interest for genes involved in cancer. We therefore applied high-resolution chromosomal conformation capture sequencing to map the three-dimensional (3D) organization of the human locus encoding the key myeloid transcription factor PU.1 in healthy monocytes and acute myeloid leukemia (AML) cells. We identified a dynamic similar to 75-kb unit (SubTAD) as the genomic region in which spatial interactions between PU.1 gene regulatory elements occur during myeloid differentiation and are interrupted in AML. Within this SubTAD, proper initiation of the spatial chromosomal interactions requires PU.1 autoregulation and recruitment of the chromatin-adaptor protein LDB1 (LIM domain-binding protein 1). However, once these spatial interactions have occurred, LDB1 stabilizes them independently of PU.1 autoregulation. Thus, our data support that PU.1 autoregulates its expression in a "hit-and-run" manner by initiating stable chromosomal loops that result in a transcriptionally active chromatin architecture.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSCRIPTION FACTORS; MYELOID-LEUKEMIA; DIFFERENTIATION; GENE; ORGANIZATION; MACROPHAGE; EXPRESSION; GENOMES; CELLS; PROGENITORS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Oct 2019 05:50 |
| Last Modified: | 07 Oct 2019 06:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13342 |
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