Transcription of immediate-early genes—as well as multiple genes affecting muscle function, cytoskeletal integrity, apoptosis control, and wound healing/angiogenesis—is regulated by serum response factor (Srf). Extracellular signals regulate Srf in part via a pathway involving megakaryoblastic leukemia 1 (Mkl1, also known as myocardin-related transcription factor A [Mrtf-a]), which coactivates Srf-responsive genes downstream of Rho GTPases. Here we investigate Mkl1 function using gene targeting and show the protein to be essential for the physiologic preparation of the mammary gland during pregnancy and the maintenance of lactation. Lack of Mkl1 causes premature involution and impairs expression of Srf-dependent genes in the mammary myoepithelial cells, which control milk ejection following oxytocin-induced contraction. Despite the importance of Srf in multiple transcriptional pathways and widespread Mkl1 expression, the spectrum of abnormalities associated with Mkl1 absence appears surprisingly restricted.

The C‐terminal activation domain (C‐TAD) of the hypoxia‐inducible transcription factors HIF‐1α and HIF‐2α binds the CH1 domains of the related transcriptional coactivators CREB‐binding protein (CBP) and p300, an oxygen‐regulated interaction thought to be highly essential for hypoxia‐responsive transcription. The role of the CH1 domain in vivo is unknown, however. We created mutant mice bearing deletions in the CH1 domains (ΔCH1) of CBP and p300 that abrogate their interactions with the C‐TAD, revealing that the CH1 domains of CBP and p300 are genetically non‐redundant and indispensable for C‐TAD transactivation function. Surprisingly, the CH1 domain was only required for an average of ∼35–50% of global HIF‐1‐responsive gene expression, whereas another HIF transactivation mechanism that is sensitive to the histone deacetylase inhibitor trichostatin A (TSAS) accounts for ∼70%. Both pathways are required for greater than 90% of the response for some target genes. Our findings suggest that a novel functional interaction between the protein acetylases CBP and p300, and deacetylases, is essential for nearly all HIF‐responsive transcription.

Worldwide, ethylene is the most produced organic compound. It serves as a building block for a wide variety of plastics, textiles, and chemicals, and a process has been developed for its conversion into liquid transportation fuels. Currently, commercial ethylene production involves steam cracking of fossil fuels, and is the highest CO2-emitting process in the chemical industry. Therefore, there is great interest in developing technology for ethylene production from renewable resources including CO2 and biomass. Ethylene is produced naturally by plants and some microbes that live with plants. One of the metabolic pathways used by microbes is via an ethylene-forming enzyme (EFE), which uses α-ketoglutarate and arginine as substrates. EFE is a promising biotechnology target because the expression of a single gene is sufficient for ethylene production in the absence of toxic intermediates. Here we present the first comprehensive review and analysis of EFE, including its discovery, sequence diversity, reaction mechanism, predicted involvement in diverse metabolic modes, heterologous expression, and requirements for harvesting of bioethylene. A number of knowledge gaps and factors that limit ethylene productivity are identified, as well as strategies that could guide future research directions.

CREB is a key mediator of cAMP‐ and calcium‐inducible transcription, where phosphorylation of serine 133 in its Kinase‐Inducible Domain (KID) is often equated with transactivation. Phospho‐Ser133 is required for CREB to bind the KIX domain of the coactivators CBP and p300 (CBP/p300) in vitro , although the importance of this archetype coactivator interaction for endogenous gene expression is unclear. Here, we show that the CREB interaction with KIX is necessary for only a part of cAMP‐inducible transcription and CBP/p300 recruitment. Surprisingly, individual cAMP‐inducible genes with CREB bound at their promoters differed in their reliance on KIX and none examined showed complete dependence. Alternatively, we found that arginine 314 (Arg314) in the CREB basic‐leucine zipper (bZIP) domain contributed to CBP/p300 recruitment and KIX‐independent CREB transactivation function. This implicates Transducer Of Regulated CREB (TORC), an unrelated cAMP‐responsive coactivator that binds via Arg314, and which can bind CBP/p300, in these functions. Interestingly, KIX was also required for the full cAMP induction of a gene that did not require CREB. Thus, individual CREB‐target gene context dictates the relative contribution of at least two different cAMP‐responsive coactivation mechanisms.