Preferred sequences for DNA recognition by the TAL1 helix-loop-helix proteins

Journal Article · Tue Feb 01 04:00:00 EST 1994 · Molecular and Cellular Biology

OSTI ID:577135

Hsu, Hai-Ling; Huang, Lan; Tsan, Julia Tsou ^[1]

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1. Univ. of Texas Southwestern Medical Center, Dallas, TX (United States); and others

Tumor-specific activation of the TAL1 gene is the most common genetic alteration seen in patients with T-cell acute lymphoblastic leukemia. The TAL1 gene products contain the basic helix-loop-helix (bHLH) domain, a protein dimerization and DNA-binding motif common to several known transcription factors. A binding-site selection procedure has now been used to evaluate the DNA recognition properties of TAL1. These studies demonstrate that TAL1 polypeptides do not have intrinsic DNA-binding activity, presumably because of their inability to form bHLH homodimers. However, TAL1 readily interacts with any of the known class A bHLH proteins (E12, E47, E2-2, and HEB) to form heterodimers that bind DNA in a sequence-specific manner. The TAL1 heterodimers preferentially recognize a subset of E-box elements (CANNTG) that can be represented by the consensus sequence AACAGATGGT. This consensus is composed of half-sites for recognition by the participating class A bHLH polypeptide (AACAG) and the TAL1 polypeptide (ATGGT). TAL1 heterodimers with DNA-binding activity are readily detected in nuclear extracts of Jurkat, a leukemic cell line derived from a patient with T-cell acute lymphoblastic leukemia. Hence, TAL1 is likely to bind and regulate the transcription of a unique subset of subordinate target genes, some of which may mediate the malignant function of TAL1 during T-cell leukemogenesis. 48 refs., 10 figs.

• OSTI ID: 577135
• Journal Information: Molecular and Cellular Biology, Journal Name: Molecular and Cellular Biology Journal Issue: 2 Vol. 14; ISSN 0270-7306; ISSN MCEBD4
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
DIMERIZATION
DNA
DNA SEQUENCING
GENE REGULATION
GENES
LEUKEMIA
LEUKEMOGENESIS
OLIGONUCLEOTIDES
PATIENTS
POLYMERASE CHAIN REACTION
POLYPEPTIDES
PROTEINS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRANSCRIPTION
TRANSCRIPTION FACTORS