Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have used a purified recombinant chromatin assembly system, including ACF (Acf-1 + ISWI) and NAP-1, to examine the role of histone acetylation in ATP-dependent chromatin remodeling. The binding of a transcriptional activator (Gal4-VP16) to chromatin assembled using this recombinant assembly system dramatically enhances the acetylation of nucleosomal core histones by the histone acetyltransferase p300. This effect requires both the presence of Gal4-binding sites in the template and the VP16-activation domain. Order-of-addition experiments indicate that prior activator-meditated, ATP-dependent chromatin remodeling by ACF is required for the acetylation of nucleosomal histones by p300. Thus, chromatin remodeling, which requires a transcriptional activator, ACF and ATP, is an early step in the transcriptional process that regulates subsequent core histone acetylation. Glycerol gradient sedimentation and immunoprecipitation assays demonstrate that the acetylation of histones by p300 facilitates the transfer of H2A-H2B from nucleosomes to NAP-1. The results from these biochemical experiments suggest that (1) transcriptional activators (e.g., Gal4-VP16) and chromatin remodeling complexes (e.g., ACF) induce chromatin remodeling in the absence of histone acetylation; (2) transcriptional activators recruit histone acetyltransferases (e.g., p300) to promoters after chromatin remodeling has occurred; and (3) histone acetylation is important for a step subsequent to chromatin remodeling and results in the transfer of histone H2A-H2B dimers from nucleosomes to a histone chaperone such as NAP-1. Our results indicate a precise role for histone acetylation, namely to alter the structure of nucleosomes (e.g., facilitate the loss of H2A-H2B dimers) that have been remodeled previously by the action of ATP-dependent chromatin remodeling complexes. Thus, transcription from chromatin templates is ordered and sequential, with precise timing and roles for ATP-dependent chromatin remodeling, subsequent histone acetylation, and alterations in nucleosome structure.
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PMID:p300-mediated acetylation facilitates the transfer of histone H2A-H2B dimers from nucleosomes to a histone chaperone. 1092 4

Copper is an essential cellular cofactor that becomes toxic at high levels. Copper homeostasis is tightly regulated by opposing mechanisms that control copper import, export, and copper binding capacity within the cell. High levels of copper induce the expression of metallothioneins, small sulfhydryl-rich proteins with high metal binding capabilities that serve as neutralizers of toxic levels of metals. In yeast, the CUP1 gene encodes a copper metallothionein that is strongly induced in response to metals and other stress and is subsequently rapidly down-regulated. Activation of CUP1 is mediated by the copper-responsive transcriptional activator AceI, and also requires the histone acetylase Spt10 for full induction. We have examined the role of histone H2A in the normal regulation of the CUP1 gene. We have shown that specific H2A mutations in combination with spt10 deletions result in aberrant regulation of CUP1 expression. Certain lysine mutations in H2A alleviate the transcriptional defect in spt10 Delta strains, though CUP1 activation is still delayed in these mutants; however, CUP1 shutdown is normal. In contrast, serine mutations in H2A prevent CUP1 shutdown when combined with spt10 deletions. In addition, swi/snf mutants exhibit both impaired CUP1 induction and failure to shut down CUP1 normally. Finally, different Spt10-dependent histone acetylation events correlate with induction and shutdown. Taken together, these data indicate that CUP1 transcriptional shutdown, like induction, is an active process controlled by the chromatin structure of the gene. These results provide new insights for the role of chromatin structure in metal homeostasis.
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PMID:Histone H2A and Spt10 cooperate to regulate induction and autoregulation of the CUP1 metallothionein. 1550 26

Eukaryotic cells possess many transcriptionally regulated mechanisms to alleviate the nucleosome barrier. Dramatic changes to the chromatin structure of Drosophila melanogaster Hsp70 gene loci are dependent on the transcriptional activator, heat shock factor (HSF), and poly(ADP-ribose) polymerase (PARP). Here, we find that PARP is associated with the 5' end of Hsp70, and its enzymatic activity is rapidly induced by heat shock. This activation causes PARP to redistribute throughout Hsp70 loci and Poly(ADP-ribose) to concurrently accumulate in the wake of PARP's spread. HSF is necessary for both the activation of PARP's enzymatic activity and its redistribution. Upon heat shock, HSF triggers these PARP activities mechanistically by directing Tip60 acetylation of histone H2A lysine 5 at the 5' end of Hsp70, where inactive PARP resides before heat shock. This acetylation is critical for the activation and spread of PARP as well as for the rapid nucleosome loss over the Hsp70 loci.
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PMID:Activator-induced spread of poly(ADP-ribose) polymerase promotes nucleosome loss at Hsp70. 2217 97