Abstract
A role for variant histone H2A.Z in gene expression is now well established but little is known about the mechanisms by which it operates. Using a combination of ChIP–chip, knockdown and expression profiling experiments, we show that upon gene induction, human H2A.Z associates with gene promoters and helps in recruiting the transcriptional machinery. Surprisingly, we also found that H2A.Z is randomly incorporated in the genome at low levels and that active transcription antagonizes this incorporation in transcribed regions. After cessation of transcription, random H2A.Z quickly reappears on genes, demonstrating that this incorporation utilizes an active mechanism. Within facultative heterochromatin, we observe a hyper accumulation of the variant histone, which might be due to the lack of transcription in these regions. These results show how chromatin structure and transcription can antagonize each other, therefore shaping chromatin and controlling gene expression.
Highlights
Chromatin dynamics is well recognized as key in the regulation of nuclear processes such as gene expression, DNA replication and DNA repair, impinging on biological phenomena such as cellular differentiation as well as normal and cancer development
We show that the variant histone H2A.Z is dynamically recruited to promoter regions where it helps in the recruitment of RNA polymerase II, the enzyme responsible for the first step of gene expression
We show that H2A.Z associates randomly in the genome, but these molecules are removed during the passage of RNA polymerase II
Summary
Chromatin dynamics is well recognized as key in the regulation of nuclear processes such as gene expression, DNA replication and DNA repair, impinging on biological phenomena such as cellular differentiation as well as normal and cancer development. Incorporation of variant histones within chromatin regions is emerging as a way for cells to create specialized chromatin domains in order to mediate various cellular functions [1]. H2A.Z is required for viability in most organisms [5,6,7,8] It is necessary for early development in Xenopus, Drosophila and mouse [6,7,8], is associated with cancer progression [9,10,11,12], and is required for estrogen receptor signaling [13] and for embryonic stem cell lineage commitment [14]
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