Chromatin looping defines expression of TAL1, its flanking genes, and regulation in T-ALL

Zhou, Y., Kurukuti, S., Saffrey, P., Vukovic, M., Michie, A.M. , Strogantsev, R., West, A.G. and Vetrie, D. (2013) Chromatin looping defines expression of TAL1, its flanking genes, and regulation in T-ALL. Blood, 122(26), pp. 4199-4209. (doi: 10.1182/blood-2013-02-483875)

Full text not currently available from Enlighten.

Abstract

TAL1 is an important regulator of hematopoiesis and its expression is tightly controlled despite complexities in its genomic organization. It is frequently misregulated in T-cell acute lymphoblastic leukemia (T-ALL), often due to deletions between TAL1 and the neighboring STIL gene. To better understand the events that lead to TAL1 expression in hematopoiesis and in T-ALL, we studied looping interactions at the TAL1 locus. In TAL1-expressing erythroid cells, the locus adopts a looping “hub” which brings into close physical proximity all known TAL1 cis-regulatory elements including CTCF-bound insulators. Loss of GATA1 results in disassembly of the hub and loss of CTCF/RAD21 from one of its insulators. Genes flanking TAL1 are partly dependent on hub integrity for their transcriptional regulation. We identified looping patterns unique to TAL1-expressing T-ALL cells, and, intriguingly, loops occurring between the TAL1 and STIL genes at the common TAL1/STIL breakpoints found in T-ALL. These findings redefine how TAL1 and neighboring genes communicate within the nucleus, and indicate that looping facilitates both normal and aberrant TAL1 expression and may predispose to structural rearrangements in T-ALL. We also propose that GATA1-dependent looping mechanisms may facilitate the conservation of TAL1 regulation despite cis-regulatory remodeling during vertebrate evolution.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:West, Dr Adam and Saffrey, Dr Peter and Michie, Dr Alison and Strogantsev, Mr Ruslan and Vetrie, Professor David and Kurukuti, Dr Sreenivasulu and Vukovic, Ms Milica and Zhou, Mr Yan
Authors: Zhou, Y., Kurukuti, S., Saffrey, P., Vukovic, M., Michie, A.M., Strogantsev, R., West, A.G., and Vetrie, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Blood
Publisher:American Society of Hematology
ISSN:0006-4971
ISSN (Online):1528-0020

University Staff: Request a correction | Enlighten Editors: Update this record