Background Heading date is crucial for rice reproduction and geographic expansion. Many heading date genes are sensitive to photoperiod and jointly regulate flowering time in rice. However, it is not clear how these genes coordinate rice heading. Results Here, we performed a genetic interaction analysis among four major rice heading date genes Ghd7 , Ghd8 , OsPRR37/Ghd7.1 (hereafter PRR37 ) and Hd1 in the near-isogenic background under both natural long-day (NLD) and natural short-day (NSD) conditions. The 4-gene segregating population exhibited a large heading date variation with more than 95 days under NLD and 42 days under NSD conditions. Tetragenic, trigenic and digenic interactions among these four genes were observed under both conditions but more significant under NLD conditions. In the functional Hd1 backgrounds, the strongest digenic interaction was Ghd7 by Ghd8 under NLD but was Ghd7 by PRR37 under NSD conditions. Interestingly, PRR37 acted as a flowering suppressor under NLD conditions, while it functioned alternatively as an activator or a suppressor under NSD conditions depending on the status of the other three genes. Based on the performances of 16 homozygous four-gene combinations, a positive correlation between heading date and spikelets per panicle (SPP) was found under NSD conditions, but changed to a negative correlation when heading date was over 90 days under NLD conditions. Conclusions These results demonstrate the importance of genetic interactions in the rice flowering regulatory network and will help breeders to select favorable combinations to maximize rice yield potential for different ecological areas. Electronic supplementary material The online version of this article (10.1186/s12284-019-0314-x) contains supplementary material, which is available to authorized users.

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