Chromatin structure and its alteration play critical roles in the regulation

Chromatin structure and its alteration play critical roles in the regulation of transcription. were increased in TAF-I KD cells N-Methyl Metribuzin only during the early stages of transcription. Furthermore histone H1 KD also increased ISG transcript. TAF-I and histone H1 double KD did not show the additive effect in ISG transcription suggesting that TAF-I and histone H1 may act on the same regulatory pathway to control ISG transcription. In addition TAF-I KD and histone H1 KD affected the chromatin structure near the promoters. On the basis of these findings we propose that TAF-I and its target histone H1 are key regulators of the chromatin structure at the promoter to maintain the silent state of ISG transcription. INTRODUCTION Transcriptional regulation is accomplished mainly by the regulatory elements such as promoters and enhancers those of Rabbit polyclonal to AMDHD2. which have a variety of binding sites for sequence-specific transcription factors and specify characteristic chromatin structures mediated by nucleosome positioning specific histone modifications histone variants and other factors (1 2 For the transcription of type-I interferon (IFN)-stimulated genes (ISGs) promoters containing sequence motifs known as IFN-stimulated response element (ISRE) are the binding sites of the sequence-specific transcription factors activated by IFN stimulation. The chromatin structure and histone modification around ISRE are regulated by coactivators for ISG transcription (3 4 IFN in particular type-I IFN plays a critical role in cellular antiviral mechanisms by inducing immediate transcription of ISGs which encode proteins that not only have anti-viral activities but also affect host-cellular events such as cell death messenger ribonucleic acid (mRNA) degradation and translational arrest through the IFN signaling pathway called the JAK-STAT pathway (5). In the case of stimulation by type-I IFN the IFN-stimulated gene factor 3 (ISGF3) complex consisting of transcription factors signal transducers N-Methyl Metribuzin and activators of transcription (STAT)1 STAT2 and IFN regulatory factor 9 (IRF9) bind to ISREs in the promoters facilitating transcription initiation complex formation and thereby promoting the transcription of ISGs (3 5 In addition ISG transcription is regulated by several different kinds of coactivators (4). STATs interact with histone acetyltransferases (HATs) including p300/CBP and GCN5 and GCN5 acetylates histones on the promoter in an IFN-dependent manner (6 7 Interestingly inhibition of histone deacetylase (HDAC) activity which opposes activity of HAT leads to a global impairment of the ISG transcription (8-10). In addition pp32 a major component of the inhibitor of acetyltransferase (INHAT) complex (11) is involved in the maximal induction of ISG transcription (12). BRG1 an adenosine triphosphate (ATP)-dependent nucleosome remodeling factor and a subunit of the SWI/SNF complex interacts with STAT2 in response to IFN facilitates the chromatin remodeling of the promoter region and promotes ISG transcription (13-15). BAF200 a subunit N-Methyl Metribuzin of the SWI/SNF complex has been found to be required for selective ISG N-Methyl Metribuzin transcription (16). These studies suggest that ISG transcription via promoters is under the control of the N-Methyl Metribuzin combined effects of histone modification and specific chromatin structures. As proteins encoded by not only have anti-viral activities but also affect host-cellular events (5) the ISG transcription needs to be silenced in the IFN-unstimulated condition. However it is unclear as to how the chromatin structure of promoters is regulated to be in the unstimulated state namely the transcriptionally silent state in the absence of IFN and what kind of factors maintain the transcriptionally silent state of the promoter remains unknown. Linker histone H1 binds near to the entry and exit sites of the nucleosome core particle (NPC) which consists of a 147-base-pair (bp)-long deoxyribonucleic acid (DNA) wrapped around a histone octamer consisting of two copies each of the core histone proteins H2A H2B H3 and H4 and facilitates the higher order chromatin structure (17-19). Histone H1-dependent chromatin dynamics have been shown to be important in a variety of biological phenomena and in the transcriptional regulation of a certain gene (20-24). In addition fluorescence recovery after photobleaching analyses demonstrated that histone H1 is a highly mobile chromatin component.