The LMO2 -25 Region Harbours GATA2-Dependent Myeloid Enhancer and RUNX-Dependent T-Lymphoid Repressor Activity.

Bonadies, Nicolas; Göttgens, Berthold; Calero-Nieto, Fernando J (2015). The LMO2 -25 Region Harbours GATA2-Dependent Myeloid Enhancer and RUNX-Dependent T-Lymphoid Repressor Activity. PLoS ONE, 10(7), e0131577. Public Library of Science 10.1371/journal.pone.0131577

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Lim domain only 2 (LMO2) is a transcriptional co-factor required for angiogenesis and the specification of haematopoietic cells during development. LMO2 is widely expressed within haematopoiesis with the exception of T-cells. Failure to downregulate LMO2 during T-cell maturation leads to leukaemia, thus underlining the critical nature of context-dependent regulation of LMO2 expression. We previously identified a distal regulatory element of LMO2 (element -25) that cooperates with the proximal promoter in directing haematopoietic expression. Here we dissected the functional activity of element -25 and showed it to consist of two modules that conferred independent and cell-type specific activities: a 3' myeloid enhancer and a 5' T-cell repressor. The myeloid enhancer was bound by GATA2 in progenitors and its activity depended on a highly conserved GATA motif, whereas the T-cell repressor moiety of element -25 was bound by the Core Binding Factor in T-cells and its repressive activity depended on a highly conserved RUNT motif. Since the myeloid enhancer and nearby downstream region is recurrently involved in oncogenic translocations, our data suggest that the -25 enhancer region provides an open chromatin environment prone to translocations, which in turn cause aberrant LMO2 expression in T-cells due to the removal of the adjacent T-cell repressor.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)

UniBE Contributor:

Bonadies, Nicolas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Verena Zwahlen

Date Deposited:

17 Mar 2016 11:40

Last Modified:

17 Mar 2016 11:40

Publisher DOI:

10.1371/journal.pone.0131577

PubMed ID:

26161748

BORIS DOI:

10.7892/boris.78719

URI:

https://boris.unibe.ch/id/eprint/78719

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