Characterization of DNA-binding-dependent and -independent functions of SCL/TAL1 during human erythropoiesis.

Abstract:

:The transcription factor TAL1 has major functions during embryonic hematopoiesis and in adult erythropoiesis and megakaryocytopoiesis. These functions rely on different TAL1 structural domains that are responsible for dimerization, transactivation, and DNA binding. Previous work, most often done in mice, has shown that some TAL1 functions do not require DNA binding. To study the role of TAL1 and the relevance of the TAL1 DNA-binding domain in human erythropoiesis, we developed an approach that allows an efficient enforced wild-type or mutant TAL1 protein expression in human hematopoietic CD34(+) cells using a lentiviral vector. Differentiation capacities of the transduced cells were studied in a culture system that distinguishes early and late erythroid development. Results indicate that enforced TAL1 expression enhances long-term culture initiating cell (LTC-IC) potential and erythroid differentiation of human CD34(+) cells as shown by increased beta globin and porphobilinogen deaminase (PBGD) gene expressions and erythroid colony-forming units (CFU-Es), erythroid burst-forming units (BFU-Es), and glycophorin A-positive (GPA(+)) cell productions. Enforced expression of a TAL1 protein deleted of its DNA-binding domain (named Delta bTAL1) mimicked most TAL1 effects except for the LTC-IC enhancement, the down-regulation of the CD34 surface marker, and the GPA(+) cell production. These results provide the first functional indications of DNA-binding-dependent and -independent roles of TAL1 in human erythropoiesis.

journal_name

Blood

journal_title

Blood

authors

Ravet E,Reynaud D,Titeux M,Izac B,Fichelson S,Roméo PH,Dubart-Kupperschmitt A,Pflumio F

doi

10.1182/blood-2003-05-1689

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

3326-35

issue

9

eissn

0006-4971

issn

1528-0020

pii

2003-05-1689

journal_volume

103

pub_type

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