Genomic approaches uncover increasing complexities in the regulatory landscape at the human SCL (TAL1) locus

Dhami, P. et al. (2010) Genomic approaches uncover increasing complexities in the regulatory landscape at the human SCL (TAL1) locus. PLoS ONE, 5(2), e9059. (doi: 10.1371/journal.pone.0009059)

Abstract

The SCL (TAL1) transcription factor is a critical regulator of haematopoiesis and its expression is tightly controlled by multiple cis-acting regulatory elements. To elaborate further the DNA elements which control its regulation, we used genomic tiling microarrays covering 256 kb of the human SCL locus to perform a concerted analysis of chromatin structure and binding of regulatory proteins in human haematopoietic cell lines. This approach allowed us to characterise further or redefine known human SCL regulatory elements and led to the identification of six novel elements with putative regulatory function both up and downstream of the SCL gene. They bind a number of haematopoietic transcription factors (GATA1, E2A LMO2, SCL, LDB1), CTCF or components of the transcriptional machinery and are associated with relevant histone modifications, accessible chromatin and low nucleosomal density. Functional characterisation shows that these novel elements are able to enhance or repress SCL promoter activity, have endogenous promoter function or enhancer-blocking insulator function. Our analysis opens up several areas for further investigation and adds new layers of complexity to our understanding of the regulation of SCL expression.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bonhoure, Mr Nicolas and Chiang, Miss Kelly and Vetrie, Professor David
• Authors: Dhami, P., Bruce, A.W., Jim, J.H., Dillon, S.C., Hall, A., Cooper, J.L., Bonhoure, N., Chiang, K., Ellis, P.D., Langford, C., Andrews, R.M., and Vetrie, D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• Published Online: 05 February 2010
• Copyright Holders: Copyright © 2010 The Authors
• First Published: First published in PLoS ONE 5(2):e9059
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher