Genome-wide binding analysis unveils critical implication of B-Myb-mediated transactivation in cancers

Sep 21, 2026

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B-Myb (MYBL2) functions as a transcription factor involved in transcription regulation, cell cycle control, and tumorigenesis. The molecular basis for how B-Myb mediates transactivation across cellular contexts, and its functional relevance in cancers, remains unclear. A genome-wide approach identified B-Myb binding sites, revealing core cell-cycle regulation and cell-type-specific programs via partners such as NFY and the MuvB complex, with validated targets including KIF2C, UBE2C, and MYC.

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Ivyspring International Publisher InternationalJournal of Biological Sciences 2024; 20(12): 4691-4712. doi: 10.7150/ijbs.92607 Research Paper Genome-wide binding analysis unveils critical implication of B-Myb-mediated transactivation in cancers Chuntao Tao1,2\#, Tao Liu1,2\#, Zongrong Zhao1,2\#, Xuanqi Dou1,2, Xing Xia1,2, Kailong Du1,2, Xiaofeng Zuo1,2, Yitao Wang 1,2, Tingting Wang1,2,3􀀍, Youquan Bu1,2􀀍 1. Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China. 2. Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China. 3. Biochemistry and Molecular Biology Laboratory, Experimental Teaching and Management Center, Chongqing Medical University, Chongqing 401331, China. \# These authors contributed equally to this work. 􀀍 Corresponding authors: Prof. Youquan Bu and Dr. Tingting Wang, Department of Biochemistry and Molecular Biology, Chongqing Medical University, 1\# Yixueyuan Road, Yuzhong District, Chongqing 400016, [P. R. China. Email: buyqcn@cqmu.edu.cn](P. R. China. Email: buyqcn@cqmu.edu.cn), [buyqcn@aliyun.com](buyqcn@aliyun.com). © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [http://ivyspring.com/terms](http://ivyspring.com/terms) for full terms and conditions. Received: 2023.11.25; Accepted: 2024.08.17; Published: 2024.09.03 Abstract B-Myb, also known as MYB proto-oncogene like 2 (MYBL2), is an important transcription factor implicated in transcription regulation, cell cycle and tumorigenesis. However, the molecular mechanism underlying B-Myb-controlled transactivation in different cell contexts as well as its functional implication in cancers remains elusive. In this study, we have conducted a comprehensive genome-wide analysis of B-Myb binding sites in multiple immortalized or cancer cell lines and identified its critical target genes. The results revealed that B-Myb regulates a common set of core cell cycle genes and cell type-specific genes through collaboration with other important transcription factors (e.g. NFY and MuvB complex) and binding to cell type-invariant promoters and cell type-specific enhancers and super-enhancers. KIF2C, UBE2C and MYC were further validated as B-Myb target genes. Loss-of-function analysis demonstrated that KIF2C knockdown inhibited tumor cell growth both in vitro and in vivo, suppressed cell motility and cell cycle progression, accompanied with defects in microtubule organization and mitosis, strongly suggesting that KIF2C is a critical regulator of cancer cell growth and mitosis, and maintains high cancer cell motility ability and microtubule dynamics. Pan-cancer transcriptomic analysis revealed that the overexpression of both B-Myb and KIF2C presents as independent prognostic markers in various types of cancer. Notably, B-Myb associates with NFYB, binds to target gene promoters, enhancers and super-enhancers, and provokes a cascade of oncogenic gene expression profiles in cancers. Overall, our results highly suggest the critical implication of B-Myb-mediated gene regulation in cancers, and the promising therapeutic and prognostic potentials of B-Myb and KIF2C for cancer diagnosis and treatment. Keywords: B-Myb, KIF2C, Transcriptional regulation, Lung adenocarcinoma, Cancer Introduction B-Myb, also known as MYB proto-oncogene like 2 (MYBL2), is a prominent member of the MYB family of transcription factors, and is implicated in the regulation of cell cycle progression, cell proliferation, cell differentiation, cell survival, and apoptosis [1-3] . It is frequently overexpressed in a broad spectrum of cancer entities, including breast cancer, non-small-cell lung cancer, colorectal cancer, neuroblastoma, osteosarcoma, etc [4-14] . Overexpression of B-Myb

FAQs

What is B-Myb (MYBL2) and why is it important in cancer?

B-Myb is a transcription factor implicated in transcription regulation, cell cycle progression, and tumorigenesis, and it is described as overexpressed across many cancer types with links to poor prognosis.

What did the study do to understand B-Myb’s role in different cancer contexts?

The study performed a comprehensive genome-wide analysis of B-Myb binding sites across multiple immortalized or cancer cell lines to identify critical target genes.

Which findings connect B-Myb activity to cancer development and progression?

Results indicate B-Myb controls both common core cell-cycle genes and cell-type-specific genes through collaboration with other transcription factors and through binding at promoters, enhancers, and super-enhancers; KIF2C knockdown reduced growth, motility, and cell-cycle progression, and pan-cancer analysis links B-Myb and KIF2C overexpression to prognostic significance.

Sep 21, 2026

Uploaded by Levi