Epigenetic modifiers: catalytic or noncatalytic, that is the question
Yimin Liu1, Haitao Li1,2,3()
. State Key Laboratory of Molecular Oncology, Beijing Frontier Research Center for Biological Structure, School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China . SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine, Shanxi Medical University, Taiyuan 030001, China . Tsinghua-Peking Center for Life Sciences, Beijing 100084, China
Fig.1 Catalytic and noncatalytic functions of SETD2. (A) A working model explaining the acting mechanisms of the wild-type (WT), catalytically dead (CD), and knockout (KO) Setd2 (created by Figdraw). SETD2 protein normally mediates the co-transcriptional H3K36me3 (denoted by circled me) through direct interaction with the hyperphosphorylated (denoted by circled P) RNA Pol II. The cross denotes the loss of catalytic activity of SETD2. The question mark denotes possible factor(s) whose recruitment or function may be facilitated by SETD2 independent of its catalytic activity. The transparent SETD2 and possible factors indicate their loss with Setd2 KO. (B) Examples of putative target genes of SETD2 relevant to its catalytic and noncatalytic functions. Many of the highly interrupted collagen genes are downregulated in the Setd2-CD and Setd2-KO mice, whereas the allantois-specific 5′ Hoxa cluster genes are differentially regulated in these two models. Dashed line rectangle denotes the whole cluster of genes. (C) A summary of several recent studies, implying possible determinants of the epigenetic modifiers for their functional dependencies on catalytic activities. Note that the epigenetic modifiers whose major functions are independent of catalytic activities tend to be involved in multiprotein complexes and to mediate functionally redundant chromatin modifications. In contrast, the epigenetic modifiers showing more catalytic dependencies tend to work alone and to mediate functionally unique chromatin modifications.
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