Rhabdoid Tumor : Role of SMARCB1 (INI1)

Comments:
Interaction of SMARCB1 with Polycomb Pathway: During lineage-specific differentiation, the SWI/SNF chromatin remodeling complex (and SMARCB1 as one of its key subunits) interacts with transcription factors, histone acetyltransferases and transcriptional regulators to activate expression of target genes. It results in acetylation of lysine 27 of histone H3 (H3K27 Ac).

Polycomb proteins antagonize the actions of the SWI/SNF complex. They play a key role in epigenetically silencing genes during proliferation and development. Two multiprotein repressive complexes are formed - PRC1 and PRC2. PRC2 complex contains a catalytic subunit - enhancer of zeste 2 (EZH2) - which is a histone-lysine N-methyltransferase. This complex mediates the trimethylation of lysine 27 of histone H3 (H3K27 Me3), which results in silencing of gene expression and may have a role in oncogenic transformation. SMARCB1 downregulates EZH2 and SMARCB1-deficient tumors overexpress EZH2 which is often associated with tumor progression and poor prognosis.

Image source: Kalimuthu SN, Chetty R. Gene of the month: SMARCB1. J Clin Pathol 2016; 69:484-489; used under Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license.