Optimization of protocols for studies of HDAC complexes in a synovial sarcoma model

Introduction Development of cancer has long been considered to be the consequence of a wide variety of genetic alterations such as chromosomal translocations, point mutations and deletions that alter proliferation and survival by activating oncogenes or by inactivating tumor-suppressor genes. Whereas these genetic changes constitute the basis of transformation, recent discoveries suggest additional levels of gene regulation that may play a key role in tumor heterogeneity and progression, which are generally referred to as epigenetic. The term “epigenetic” encompasses the sum of heritable modifications that do not involve changes to the underlying DNA sequence. Different mechanisms can initiate and sustain epigenetic changes and a complex interplay of these different mechanisms is beginning to be elucidated. Epigenetic modifications include: DNA methylation, which generates 5- methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), post-translational histone tail modifications, including methylation, acetylation, phosphorylation and ubiquitylation, energy-dependent nucleosomal remodeling, and long noncoding RNA regulation of local chromatin structure and chromosome organization.