Genomic approaches uncover increasing complexities in the regulatory landscape at the human SCL (TAL1) locus.
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.
Dhami
Pawandeep
P
The Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
Bruce
Alexander W
AW
Jim
Johanna H
JH
Dillon
Shane C
SC
Hall
Amanda
A
Cooper
Jonathan L
JL
Bonhoure
Nicolas
N
Chiang
Kelly
K
Ellis
Peter D
PD
Langford
Cordelia
C
Andrews
Robert M
RM
Vetrie
David
D
D000107:Acetylation; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D000076246:CCCTC-Binding Factor; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D005786:Gene Expression Regulation; D018922:HL-60 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000378:metabolism*; D020298:U937 Cells
D051792:Basic Helix-Loop-Helix Proteins; D000076246:CCCTC-Binding Factor; D006657:Histones; D008239:Lysine; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C000619697:CTCF protein, human; C067143:TAL1 protein, human