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This study investigated the regulation of gene expression in root, leaf, and grain tissues of bread wheat (Triticum aestivum L.) in response to drought and heat stresses at the grain-filling stage for the first time by transcriptome analysis. The sequencing result, obtained on a Roche 454 GS FLX+, yielded a total of 117,790,028 base reads and 8,351 unigenes with an average length of 461 bp. Through transcriptome analysis, numerous transcripts have been identified to be involved in maintaining osmotic and ionic balance, detecting and transmitting signals, modifying protein structure and function, ensuring membrane integrity and stability, and are associated with energy and carbohydrate metabolism. Against drought and hightemperature stresses, tolerance mechanisms in the root, leaf, and grain tissues differentially regulated many specific transcription factors identified. Betaine aldehyde dehydrogenase, callose synthase, cell wall-associated hydrolase, MYB33, and NAC69 transcription factors expression levels were measured with qRT-PCR. Transcriptome analysis revealed that the transcripts identified were related to osmotic and ionic balance, signal detection and transduction, modification of structural and functional proteins, cell membrane structure and stability, energy and carbohydrate metabolism, and their expression level varied according to the tissue or drought and high-temperature stress applied. [ABSTRACT FROM AUTHOR]