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Activation of the β globin locus by transcription factors and chromatin modifiers
Author(s) -
McMorrow Tara,
van den Wijngaard Arthur,
Wollenschlaeger Alex,
van de Corput Mariëtte,
Monkhorst Kim,
Trimborn Tolleiv,
Fraser Peter,
van Lohuizen Maarten,
Jenuwein Thomas,
Djabali Malek,
Philipsen Sjaak,
Grosveld Frank,
Milot Eric
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.18.4986
Subject(s) - biology , chromatin , transcription (linguistics) , locus control region , genetics , locus (genetics) , globin , transcription factor , microbiology and biotechnology , gene , enhancer , linguistics , philosophy
Locus control regions (LCRs) alleviate chromatin‐mediated transcriptional repression. Incomplete LCRs partially lose this property when integrated in transcriptionally restrictive genomic regions such as centromeres. This frequently results in position effect variegation (PEV), i.e. the suppression of expression in a proportion of the cells. Here we show that this PEV is influenced by the heterochromatic protein SUV39H1 and by the Polycomb group proteins M33 and BMI‐1. A concentration variation of these proteins modulates the proportion of cells expressing human globins in a locus‐dependent manner. Similarly, the transcription factors Sp1 or erythroid Krüppel‐like factor (EKLF) also influence PEV, characterized by a change in the number of expressing cells and the chromatin structure of the locus. However, in contrast to results obtained in a euchromatic locus, EKLF influences the expression of the γ‐ more than the β‐globin genes, suggesting that the relief of silencing is caused by the binding of EKLF to the LCR and that genes at an LCR proximal position are more likely to be in an open chromatin state than genes at a distal position.