Hypoxic repression of endothelial nitric-oxide synthase transcription is coupled with eviction of promoter histones. Export

@article{citeulike:6071688, abstract = {Hypoxia elicits endothelial dysfunction, in part, through reduced expression of endothelial nitric oxide synthase (eNOS). Here we present evidence that hypoxia causes a rapid decrease in the transcription of the eNOS gene, accompanied by decreased acetylation and lysine 4 (Histone H3) methylation of eNOS proximal promoter histones. Surprisingly, we demonstrate that histones are rapidly evicted from the eNOS proximal promoter during hypoxia. We also demonstrate endothelial-specific H2A.Z incorporation at the eNOS promoter and find that H2A.Z is also evicted by hypoxic stimulation. After longer durations of hypoxia, histones are reincorporated at the eNOS promoter, but these histones lack substantial histone acetylation. Additionally, we identify a key role for the chromatin remodeler, Brg1, in reestablishing eNOS expression following reoxygenation of hypoxic cells. We posit that post-translational histone modifications are required to maintain constitutive eNOS transcriptional activity, and that histone eviction rapidly resets histone marks, and is a proximal event in the hypoxic repression of eNOS. While nucleosome eviction has been reported in models of transcriptional activation, the observation that eviction can also accompany transcriptional repression in hypoxic mammalian cells argues that eviction may be broadly relevant to both positive and negative changes in transcription.}, author = {Fish, Jason E. and Yan, Matthew S. and Matouk, Charles C. and St Bernard, Rosanne and Ho, Jyun David D. and Gavryushova, Anna and Srivastava, Deepak and Marsden, Philip A.}, citeulike-article-id = {6071688}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M109.067868}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19880524}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19880524}, day = {30}, doi = {10.1074/jbc.M109.067868}, issn = {1083-351X}, journal = {The Journal of biological chemistry}, keywords = {coupled, endothelial, eviction, histones, hypoxic, is, nitric-oxide, of, promoter, repression, synthase, transcription, with}, month = {October}, posted-at = {2009-11-04 22:28:56}, priority = {2}, title = {Hypoxic repression of endothelial nitric-oxide synthase transcription is coupled with eviction of promoter histones.}, url = {http://dx.doi.org/10.1074/jbc.M109.067868}, year = {2009} }

TY - JOUR ID - citeulike:6071688 L3 - citeulike-article-id:6071688 N2 - Hypoxia elicits endothelial dysfunction, in part, through reduced expression of endothelial nitric oxide synthase (eNOS). Here we present evidence that hypoxia causes a rapid decrease in the transcription of the eNOS gene, accompanied by decreased acetylation and lysine 4 (Histone H3) methylation of eNOS proximal promoter histones. Surprisingly, we demonstrate that histones are rapidly evicted from the eNOS proximal promoter during hypoxia. We also demonstrate endothelial-specific H2A.Z incorporation at the eNOS promoter and find that H2A.Z is also evicted by hypoxic stimulation. After longer durations of hypoxia, histones are reincorporated at the eNOS promoter, but these histones lack substantial histone acetylation. Additionally, we identify a key role for the chromatin remodeler, Brg1, in reestablishing eNOS expression following reoxygenation of hypoxic cells. We posit that post-translational histone modifications are required to maintain constitutive eNOS transcriptional activity, and that histone eviction rapidly resets histone marks, and is a proximal event in the hypoxic repression of eNOS. While nucleosome eviction has been reported in models of transcriptional activation, the observation that eviction can also accompany transcriptional repression in hypoxic mammalian cells argues that eviction may be broadly relevant to both positive and negative changes in transcription. JF - The Journal of biological chemistry SN - 1083-351X TI - Hypoxic repression of endothelial nitric-oxide synthase transcription is coupled with eviction of promoter histones. KW - coupled KW - endothelial KW - eviction KW - histones KW - hypoxic KW - is KW - nitric-oxide KW - of KW - promoter KW - repression KW - synthase KW - transcription KW - with AU - Fish, Jason AU - Yan, Matthew AU - Matouk, Charles AU - St Bernard, Rosanne AU - Ho, Jyun David AU - Gavryushova, Anna AU - Srivastava, Deepak AU - Marsden, Philip PY - 2009/10/30/ UR - http://dx.doi.org/10.1074/jbc.M109.067868 ER -