In order to study the role of histone modifications (H3 acetylation/methylation) in leaf rust resistance, we utilized two NILs (HD2329 with and without Lr28) which were inoculated at seedling stage with a virulent pathotype 77-5 of P. triticina. Immuno-precipitated DNA from the seedlings of the NILs was isolated before inoculation (0hbi) and 96 h after inoculation (96hai). For immunoprecipitation, two acetylation (H3K4/K9ac) marks were used for ChIP-PCR and two methylation (H3K4/K27me3) marks for ChIP-seq. ChIP-qPCR was conducted to examine the role of two histone acetylation marks in the regulation of the expression of six selected genes (N-acetyltransferase, WRKY 40, WRKY 70, ASR1, peroxidase 12 and sarcosine oxidase) involved in wheat-rust pathosystem. For two out of six genes (N-acetyltransferase and peroxidase12), changes in enrichment largely matched with changes in H3K4/H3K9 acetylation patterns of the proximal and distal promoters. Enrichment of both the marks matched with higher expression of N-acetyltransferase in susceptible NIL (at 96 hai) and the deacetylation (H3K4ac) largely matched with reduced gene expression in resistant NIL (at 96 hai). In peroxidase12, enrichment with H3K4ac and H3K9ac largely matched with higher expression in both the NILs. In the remaining four genes, changes in H3 acetylation did not always match with gene expression levels indicating complexity in the regulation of the expression of these remaining four genes, which may be controlled by other epigenetic/genetic regulatory mechanisms that need further analysis. Genome-wide ChIP-Seq allowed identification of differential binding sites [high affinity (HA) and low affinity (LA)] in comparison of treatments involving the two NILs. For H3K4me3 (activation mark), more HA sites were identified in compatible interaction indicating that susceptibility is mainly controlled by activation of a large number of genes. In incompatible interaction, more LA sites were observed for H3K4me3 and more HA sites for H3K27me3 (repressor mark) indicating that resistance is mainly controlled by suppression of a number of genes that are probably involved in susceptibility. Overall, the results indicated the involvement of histone acetylation and methylation marks in regulation of gene expression during wheat-leaf rust pathosystem. Common genes in ChIP-Seq and RNA-Seq are being further examined to determine the role of histone methylation in the gene expression during compatible and incompatible interaction.