Post-translational modifications of histones, such as acetylation and methylation, have a pivotal role in regulating gene expression and cell growth. To elucidate the different roles and importance of H3K4 and H3K36 modifications in expression of inducible genes such as Cal1, SSA3, PHO5 and the growth of yeast cell, we constructed three different yeast mutant strains carrying mutations of lysine 4, 36, or both to leucine in the histone H3 tail. and sensitive assay under the conditions of high temperature, NaCl, caffeine, 6-AU, or other conditions were carried out to characterize the effects of these mutations on cell growth and transcription levels of GAL1, SSA3 and PHO5. The results showed that three histone methylation mutants exhibited more severe growth defects and slower activation of GAL1, SSA3 and PHO5 than those of wild type; H3K4L/H3K36L double mutant strain D436 has the most severe phenotype. H3K4L mutants S4 exhibited more severe defects than those of H3K36L S36 mutants, especially at high temperature and high NaCl stresses. These results show that H3K4L and H3K36L are important for the growth and survival of yeast in unfavorable conditions, and that different mutations have different effects on the expression of single inducible gene, whereas the same mutation has different effects on the activation of different inducible genes in vivo. The post-translational modification of H3K4 is more important than H3K36 on the adaptation to harsh condition for yeast cell. The growth defects of histone mutant strains might arise from the slow activation of inducible gene essential for survival at harsh conditions.