Abstract
Chromodomain helicase DNA-binding (CHD) chromatin remodelers regulate transcription and DNA repair. They govern cell-fate decisions during embryonic development and are often deregulated in human pathologies. Chd1-8 show upon germline disruption pronounced, often developmental lethal phenotypes. Here we show that contrary to Chd1-8 disruption, Chd9–/–animals are viable, fertile and display no developmental defects or disease predisposition. Germline deletion of Chd9 only moderately affects gene expression in tissues and derived cells, whereas acute depletion in human cancer cells elicits more robust changes suggesting that CHD9 is a highly context-dependent chromatin regulator that, surprisingly, is dispensable for mouse development.
Highlights
Normal organismal development requires accurate transcriptional control
Since Chd9 is highly expressed in murine embryonic fibroblasts (MEFs), we examined its requirement for cell proliferation and transformation
Chd9 deletion did not affect proliferation under normal culture conditions, or anchorage-independent growth of RasV12/Myc–or RasV12/E1a–transformed MEFs (S9 Fig). These results indicate that Chd9 deletion does not affect latency or histopathological features of EμMyc-driven lymphomagenesis nor does it modulate the oncogenic transformation of MEFs
Summary
Normal organismal development requires accurate transcriptional control. This is achieved by myriad of transcription factors and chromatin regulators that act in concert to control expression of the right genes at the right time. Chromodomain helicase DNA-binding enzymes belong to the superfamily of chromatin remodelers that control nucleosomal structure and phasing to regulate gene expression and DNA repair They contain hallmark amino-terminal double chromodomains and central SNF2 helicase-like ATPase domains, allowing nucleosome recognition and remodeling [1]. The CHD enzymes have limited DNA-specificity and rely on specific histone modifications and transcription factors for recruitment to target loci [2]. Based on their constituent domains, they are classified into three subfamilies: subfamily I (CHD1 and CHD2), subfamily II (CHD3, CHD4 and CHD5) and subfamily III (CHD6, CHD7, CHD8 and CHD9)
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