Steroid receptor coactivator-1 is a histone acetyltransferase

The C terminal domain of SRC-1 contains two intrinsic transactivation domains: AD1 and AD2. The AD1 domain is required for the recruitment of secondary coactivators, such as cAMP response element binding protein (CREB)-binding protein (CBP) and the histone acetyltransferase p300 (Figure 1 ). Once SRC-1 has complexed with its ligand-bound receptor at the DNA, it must bring in additional proteins such as CBP and p300 to acetylate histone residues within the enhancer and promoter regions of the target gene so that transcription can successfully occur. In vitro transcription assays from chromatin-assembled templates have demonstrated that the interaction of p300 with the AD1 domain of SRC-1 is essential for SRC-1-mediated coactivation of ERα [ 32 ]. Furthermore, observations from the p300 protein structure have confirmed that it is the SRC-1 interacting domain and not the ERα-interacting domain, that is essential for p300-mediated coactivation of ERα [ 32 ]. Additional experiments have demonstrated that the C terminus of SRC-1 and also SRC-3 have intrinsic histone acetyltransferase activity (HAT); however, it remains unclear if such HAT activity is significant for target gene activation as the SRC-1 intrinsic HAT activity is much weaker than that in the CBP/p300 proteins [ 33 , 34 ]. SRC-1 also uses its AD1 domain to interact directly or indirectly via CBP/p300 with another HAT protein known as p/CAF (Figure 1 ). p/CAF primarily acetylates histone H3 and H4 to further facilitate chromatin remodeling at the site of NR target genes [ 35 ].

Awareness and educational efforts are working to help prevent anabolic steroid abuse in schools and communities. The Adolescents Training and Learning to Avoid Steroids (ATLAS) and the Athletes Targeting Healthy Exercise and Nutrition Alternatives (ATHENA) programs, funded by the NIDA, and supported by the Oregon Health & Science University programs is teaching athletes that they do not need steroids to build powerful muscles and improve athletic performance. These programs provide weight-training and nutrition alternatives, increase healthy behaviors, less likelihood to try steroids, and less likelihood to engage in other dangerous behaviors such as drinking and driving, use of marijuana and alcohol , and and improved body image. Bother Congress and the Substance Abuse and Mental Health Services Administration endorsed these model prevention programs. 4

Steroid receptor coactivator-1 is a histone acetyltransferase

steroid receptor coactivator-1 is a histone acetyltransferase

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