Skip to main content
padlock icon - secure page this page is secure

Sequence Determinants of DNA Binding by the Hematopoietic Helix-Loop-Helix Transcription Factor TAL1: Importance of Sequences Flanking the E-Box Core

Buy Article:

$46.00 + tax (Refund Policy)

TAL1 is a helix-loop-helix transcription factor that is essential for hematopoiesis. In vitro DNA binding site selection experiments have previously identified the preferred binding site for TAL1 heterodimers as AACAGATGGT. TAL1 homodimers do not bind DNA with significant affinity. A subset of other E-box sequences is also bound by TAL1 heterodimers. Here, we present an analysis of TAL1 heterodimer DNA binding specificity, using E-boxes derived from genomic clones, which were isolated by immunoadsorption of K562 erythroleukemia cell chromatin with a TAL1 antibody. We show that TAL1 heterodimer binding to a CAGATG E-box is strongly modulated by nucleotides flanking the E-box. A 10 base pair element consisting of the CAGATG E-box and two flanking nucleotides in both the 5′ and 3′ direction is sufficient for high-affinity binding. Certain mutations of nucleotides in either the 5′ (-1 and -2) or 3′ (+1 and +2) direction strongly inhibit binding. The importance of flanking nucleotides also exists in the context of nonpreferred E-boxes recognized by TAL1 heterodimers. Although there are no known target genes for TAL1, the regulatory regions of several genes involved in hematopoiesis contain the preferred E-box CAGATG. However, based on our results, the E-boxes in these potential target genes contain flanking sequences that would be expected to significantly reduce TAL1 heterodimer binding in vitro. Thus, additional stabilizing forces, such as protein-protein interactions between TAL1 heterodimers and accessory factors, may be required to confer high-affinity TAL1 heterodimer binding to such sequences.
No References
No Citations
No Supplementary Data
No Article Media
No Metrics

Keywords: E-box; Erythroid; Helix-loop-helix; Hematopoiesis; Leukemogenesis; SCL; T-ALL; TAL1; Transcription factor

Document Type: Research Article

Publication date: January 1, 1998

More about this publication?
  • Gene Expression, The Journal of Liver Research will publish articles in all aspects of hepatology. Hepatology, as a research discipline, has seen unprecedented growth especially in the cellular and molecular mechanisms of hepatic health and disease, which continues to have a major impact on understanding liver development, stem cells, carcinogenesis, tissue engineering, injury, repair, regeneration, immunology, metabolism, fibrosis, and transplantation. Continued research and improved understanding in these areas will have a meaningful impact on liver disease prevention, diagnosis, and treatment. The existing journal Gene Expression has expanded its focus to become Gene Expression, The Journal of Liver Research to meet this growing demand. In its revised and expanded scope, the journal will publish high-impact original articles, reviews, short but complete articles, and special articles (editorials, commentaries, opinions) on all aspects of hepatology, making it a unique and invaluable resource for readers interested in this field. The expanded team, led by an Editor-in-Chief who is uniquely qualified and a renowned expert, along with a dynamic and functional editorial board, is determined to make this a premier journal in the field of hepatology.
  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more