Establishment and maintenance of gene expression states is central to development and differentiation. Transcriptional and epigenetic mechanisms interconnect in poorly understood ways to determine these states. We explore these mechanisms through dissection of the regulation of Arabidopsis thaliana FLOWERING LOCUS C (FLC). FLC can be present in a transcriptionally active state marked by H3K36me3 or a silent state marked by H3K27me3. Here, we investigate the trans factors modifying these opposing histone states and find a physical coupling in vivo between the H3K36 methyltransferase, SDG8, and the H3K27me3 demethylase, ELF6. Previous modeling has predicted this coupling would exist as it facilitates bistability of opposing histone states. We also find association of SDG8 with the transcription machinery, namely RNA polymerase II and the PAF1 complex. Delivery of the active histone modifications is therefore likely to be through transcription at the locus. SDG8 and ELF6 were found to influence the localization of each other on FLC chromatin, showing the functional importance of the interaction. In addition, both influenced accumulation of the associated H3K27me3 and H3K36me3 histone modifications at FLC. We propose the physical coupling of activation and derepression activities coordinates transcriptional activity and prevents ectopic silencing.epigenetic regulation | histone modifications | histone methyltransferase | histone demethylase | FLOWERING LOCUS C C hromatin-based transcriptional activity is particularly important in multicellular organisms, where cells differentiate into very different developmental states. Transcriptional states are induced by internal developmental signals or triggered by environmental conditions and are then epigenetically maintained through many cell divisions. Considerable evidence suggests that opposing histone modifications mark different transcriptional states (1-6). However, there is still great debate as to how histone-based transcriptional states are initially established and maintained through development (7,8). We used Arabidopsis FLOWERING LOCUS C (FLC) as a model gene to explore histone-based transcriptional regulation and epigenetic memory. Local chromatin states are critical for quantitatively controlling FLC expression (9). Active FLC expression requires functional FRIGIDA (FRI) and a set of histone modifying Trithorax homologs, Complex Proteins Associated with Set1 (COMPASS), RNA polymerase II Associated Factor 1 complex (PAF1C), and SET DOMAIN GROUP 8 (SDG8), the major H3K36 methyltransferase (10-17). Repression of FLC requires either the autonomous pathway, which coordinately influences transcriptional initiation and elongation with associated chromatin modulation, or vernalization, the cold-induced Polycomb silencing (18-21). Both of these involve accumulation of high levels of H3K27me3 at FLC (20-22). A series of FLC antisense transcripts (COOLAIR) contribute to these repression pathways (18,(23)(24)(25)(26) Opposing H3K36me3 and H3K27me3 states are particularly ...