One limitation of this work is the inherent variability of the samples in disease etiology and treatment. However, to make our study etiologically homogenous, we chose DCM patients that reported no family history of the disease. Moreover, the patients selected in this study were on conventional therapy, and certain drugs may have influenced the levels of ER proteins. Furthermore, our tissue samples were confined to the transmural left ventricle apex, so our findings cannot be generalized to all layers and regions of the left ventricle. It is also noteworthy that this study was carried out using a high human sample size of both pathological and CNT hearts, making our results applicable for both DCM and ICM population. RNAi is a widely conserved process in eukaryotes characterised by small RNAs bound by Argonaute effector proteins which act as guides to target homologous sequences for repression. RNAi can act post-transcriptionally to regulate gene expression either by translational inhibition or transcript cleavage. In addition, RNAi can also mediate DNA and PFI-2 chromatin modifications which cause transcriptional silencing and heterochromatin formation. RNAi-directed heterochromatin XMD16-5 formation is critical for centromere function in the fission yeast, Schizosaccharomyces pombe. This process is well characterised in S. pombe due in to its genetic tractability and the fact that it encodes only single non-essential genes involved in this pathway. In fission yeast, the main domains of heterochromatin are found at centromeres, telomeres and the silent mating-type locus. Despite the fact that marker genes inserted within centromeric repeats are transcriptionally silenced, it is known that the repeats themselves are bi-directionally transcribed by RNA polymerase II during S phase. These non-coding centromere transcripts generate double-stranded RNA which is processed by the ribonuclease enzyme Dicer into 22�C 25 bp small interfering RNAs. Centromeric siRNAs act to guide the Argonaute/Ago1 effector protein, a component of the RNA-Induced Transcriptional Silencing complex, to homologous sequences.