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Individual LCR hypersensitive sites cooperate to generate an open chromatin domain spanning the human β‐globin locus
Author(s) -
Li Guolong,
Lim KimChew,
Douglas Engel James,
Bungert Jörg
Publication year - 1998
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.1998.00200.x
Subject(s) - locus control region , chromatin , biology , locus (genetics) , hypersensitive site , dnase i hypersensitive site , genetics , gene , globin , nuclease , transgene , chia pet , deoxyribonuclease i , transcription (linguistics) , chromosome conformation capture , microbiology and biotechnology , promoter , gene expression , chromatin remodeling , enhancer , base sequence , linguistics , philosophy
Background The human β‐globin locus control region (LCR) is composed of five DNase I hypersensitive (HS) sites located 5′ to the multiple genes it regulates. The LCR has been shown to comprise, among other essential properties, an activity that is required for generating a chromatin structure which renders the entire β‐globin gene locus accessible to exogenous nucleases. This nuclease‐sensitive state is generally believed to be reflective of the chromatin environment that is permissive for transcriptional activation of the globin genes. Results Here we show, in mice bearing intact YAC transgenes that encompass the whole human β‐globin locus, that the deletion of individual core LCR HS sites negatively affects the ability of the LCR to confer this open chromatin conformation throughout the locus, and when analysed in concert with the effect that these same mutations have on transcription, the data show that the chromatin opening activity is a necessary, but not sufficient, prerequisite for globin gene expression. The results also show that after deletion of individual hypersensitive sites, the mutated LCR is no longer able to provide an accessible chromatin environment that is independent from the site of YAC transgene integration. Conclusions These experiments provide further evidence for the hypothesis that the HS sites must act cooperatively to fulfil the multiple functions that are attributable to the LCR.