Finding Histone Modification Enzyme in Heart De-velopment after Reprogramming of Fibroblast into Cardio-myocyte

Objective: Cardiac cells have limited proliferation capacity and transplantation is a possibility that it is not always a good strategy, due to risk of tumor formation, so it is highly in demand to directly reprogram fibroblasts to cardiomyocyte. Some previous reports showed that fibroblast can be converted to the cardiac muscle by either a combination of transcription factors or the addition of miRNAs. Moreover, recent research implements a set of chemicals to successfully convert fibroblast to cardiac. This conversion includes opening chromatin struc-ture by histone-modifying enzymes to express cardiac-specific genes. In thishis study, we identified histone modification en-zyme which should be expressed during development of the heart. To find this, we utilized an online database from direct conversion by TFs and Chemicals in a few days after repro-gramming (۶ datasets and ۱ dataset, respectively).Materials and Methods: First, differentially expressed genes were extracted from NCBI using GEO۲R online program. Next, histone modification enzymes (methylation, acetyla-tion, phosphorylation, ubiquitination) and heart development enzymes were extracted from AmiGO to have experimentally validated gene names. Then, genes which are expressed with a fold change above ۱ and p value less than ۰.۰۵ were identified and compared with genes list from Amigo. Finally, we obtained a number of validated DEGs related to histone modification during the early stage of reprogramming to cardiac muscles.Results: Clustering of DEGs showed that most of them were related to histone acetylation and methylation. Only one gene was found as a histone phosphorylation enzyme and there was no histone ubiquitination enzyme among them.Conclusion: These findings would be helpful to illustrate key histone modification enzymes which help to continue repro-gramming by expression of cardiac development genes. More-over, generating functional heart cells can maintain their fea-tures after induction. Hence, these cells would be replaceable by non-functional cardiac muscles without losing their capacity to remain stable.

کلیدواژه ها:

Heart Development ، Histone Modification ، Gene Ex-pression