The stage sequence of cell proliferation is commonly referred to as the cell cycle, which is divided into the DNA synthesis phase(S phase) and the mitotic separation phase(M phase), with two intermediate gap phases(G1 phase and G2 phase) before the S and M phases. So what are the design ideas for the cell cycle?

Next, we’ll share a paper published on Nucleic Acids Research, with an impact of 16.7, hoping to inspire you from difference aspects.

1. Research background

1.1 CARM1 is a type I arginine methyltransferase that has been demonstrated to play a vital role in numerous cellular processes, including transcription, DNA damage response, pre-mRNA splicing, cell cycle progression, and cell differentiation.

1.2 The NuRD complex(Nucleosome Remodeling and Deacetylase) has been identified as a large multi-subunit complex that couples ATP-dependent chromatin remodeling with histone deacetylase activity.

1.3 Alterations in NuRD activity have been confirmed to cause developmental defects, cancer, and accelerated aging.

1.4 Transcription factors and co-factors, such as GATA1/FOG1, SALL1, cJUN, IKAROS, and ZMYND8, have been verified to recruit the NuRD complex to specific gene loci under particular conditions.

2. Technical routes

3. Research results

(1) CARM1 interacts with the NuRD complex through GATAD2A

(2) CARM1 hypermethylates GATAD2A/2B within the NuRD complex

(3) CARM1 and the NuRD complex co-occupy numerous chromatin loci

(4) CARM1 and NuRD activate multiple cell cycle genes and promote cell cycle progression in a CARM1 enzymatic activity-dependent manner

(5) CARM1-mediated GATAD2A methylation regulates NuRD chromatin binding, transcriptional activation of cell cycle genes, and cell cycle progression

(6) CARM1-mediated GATAD2A methylation is essential for breast cancer cell growth both in vitro and in vivo

(7) Targeting CARM1 with its inhibitor suppresses breast cancer cell growth in vitro and in vivo

4. Conclusion

The authors report that CARM1 directly interacts with GATAD2A/2B subunits of the NuRD complex. They localize at gene promoter regions and mediate transcriptional activation of numerous genes related to cell cycle control. CARM1-mediated gene activation requires methylation of a stretch of arginine residues on GATAD2A/2B by CARM1. To highlight the biological significance of CARM1-mediated GATAD2A/2B methylation and transcriptional events, upregulation of both CARM1 and NuRD is observed in clinical breast cancer samples, and knockdown of CARM1 and NuRD apparently mitigates breast cancer cell growth in vitro and tumorigenesis in vivo.These findings reveal a gene group dependent on the CARM1 “highly methylated” key chromatin remodeling complex NuRD, and targeting NuRD methylation provides a promising therapeutic strategy for clinical treatment of breast cancer.