Mammals transcriptional activity

H2A Barr body-deficient (Bbd) is an evolutionary relatively young histone variant sharing only about 48% amino acid sequence similarity to H2A. This histone variant appears to be specific for mammals (Chadwick and Willard 2001). As indicated by the name, the transcriptionally inactive and highly condensed X chromosome in female mammals (also known as Barr body ) is depleted for H2A , while this variant is detectable in autosomes and the active sex chromosomes. This observation suggested that H2A is linked to transcriptionally active euchromatin. H2A cofractionates in sedimentation centrifugation with hyper-acetylated histone H4, further corroborating that it associates with transcriptionally active euchromatin. 

Lastly, there are phosphorylation events in both Drosophila and mammals for which the function and associated kinases have not been identified as mentioned above, the kinase(s) that rhythmically phosphorylates Drosophila and mammalian CLK is not yet known, and it will be important to determine whether phosphorylation of CLK influences its transcriptional activity or its ability to bind to DNA. Although CKle modifies mammalian CRYl, CRY2 and BMALl in vitro (Eide et al 2002), and CKld will similarly phosphorylate some mammalian PER proteins (Camacho et al 2001), none of these activities have been securely established in vivo. 

Guarente, L., UASs and enhancers Common mechanism of transcriptional activation in yeast and mammals. Cell 52 303-305, 1988. 

In the slime mould, Dictyostelium discoideum, a STAT-like DNA-binding protein, DIF (the differentiation-inducing factor), is expressed. DIF is about 700 amino-acid residues long, and has substantial homology with mammalian STATs. DIF is, like STAT, activated by phosphorylation of tyrosines. It is essential for differentiation of the stalk cells of D. discoideum A The long evolutionary path that the STATs have travelled from Dictyostelium to mammals underlines their conserved and essential role as signal transmitters and transcriptional activators in early development. 

Histone H4 is the substrate for the type I enzymes Rmtl (yeast) andPRMTl (mammals). Both PRMTs methylate R3 in the histone tail. In mammals, this modification also results in transcriptional activation, as R3 methylation of histone H4 results in subsequent acetylation of the H4 tail (Wang et al., 2001). 

Retinoic acid is a hydrophobic molecule able to diffuse across the plasmalemma. Its mechanism of action is similar to that of the steroid hormones (see Section 10.1). It binds to nuclear receptors, which act as transcriptional activators. Two families of retinoic acid and retinoid receptors, RAR and RXR, have been identified in mammals and domestic fowl. The RAR family includes RAR-a, RAR-j8, RAR-y and RAR-d, and the RXR includes RXR-a, RXR-p and RXR-y (Smith Eichele, 1991 Gudas, 1994). Each gene is able to form multiple transcripts, probably by alternative splicing for example, RAR-y forms seven transcripts, and three (3.2, 3.4 and 4.6 kb). 

Commercial DDT and DDD contain o,p-DDT [ 1,1,1-trichloro-2-(c -chlorophenyl)-2-(p-chlorophenyl)] ethane and o,p-DDD [l,l-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)] ethane isomers ( 10-20%), which are chiral [28]. Investigations have demonstrated the oestrogenic activity of o,p-DDT in fish and mammals [29-34]. It is also known that the —)-o,p-DDT enantiomer is a more active oestrogen mimic than the (+)-enantiomer in rats [35, 36]. Subsequently, Hoekstra etal. [37] reported a yeast-based assay to assess the enantiomer-specific transcriptional activity of DDT with... 

Adenylate cyclase was identified as the primary Ras target in yeast (Saccha-romyces cerevisiae) [56] but it took a while before in 1993 several groups independently found Raf to be the effector of Ras in mammals [41-44]. Shortly afterwards it was realized that this is not the only target of Ras but up until now it appears to be the most prominent one. Raf is a Ser/Thr-specific protein kinase which phosphorylates and thereby activates Mek which in turn phosphorylates and activates Erk, leading to an amplification of the signal. Erk, also termed MAPK, has a plethora of phosphorylation targets, the most important of which are transcription factors such as Elk-1, leading to activation of the transcription machinery in the nucleus. 

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