American Journal of Cancer Prevention
ISSN (Print): 2328-7314 ISSN (Online): 2328-7322 Website: Editor-in-chief: Nabil Abdel-Hamid
Open Access
Journal Browser
American Journal of Cancer Prevention. 2022, 9(1), 4-9
DOI: 10.12691/ajcp-9-1-2
Open AccessArticle

The PCAF/WSTF/MOF Complex Regulates H3K9ac and H4K16ac in Breast Cancer Cells

Ya-qi Wang1, , Shunli-li Zhang1, Jing-hua Zhang2, , Shuqing Wang3, Hong Wang1, Yang Wang1 and Dan Li4

1Department of Surgical Oncology, Tangshan People’s Hospital, Tangshan, China

2Department of Surgical, Tangshan Women and Children’s Hospital, Tangshan, China

3College of Life Science, North China University of Science and Technology, Tangshan, China

4Cancer Institute, Tangshan People’s Hospital, Tangshan, China

Pub. Date: June 05, 2022

Cite this paper:
Ya-qi Wang, Shunli-li Zhang, Jing-hua Zhang, Shuqing Wang, Hong Wang, Yang Wang and Dan Li. The PCAF/WSTF/MOF Complex Regulates H3K9ac and H4K16ac in Breast Cancer Cells. American Journal of Cancer Prevention. 2022; 9(1):4-9. doi: 10.12691/ajcp-9-1-2


In order to study WSTF (Williams syndrome transcription factor) regulation mechanism involved in Ras signal related to breast cancer cells. Western blot was used to detect WSTF phosphorylation and histone modification levels. GST pull-down was conducted to testify the interaction between WSTF, PCAF and MOF. Acetyltransferase activity of PCAF and MOF was tested via HAT activity assay. ChIP and Real-time PCR were applied to confirm gene expression. In vivo tumor growth analysis was used to test tumor formation capability. Results revealed an interaction between WSTF, PCAF and MOF. WSTF phosphorylation increased following Ras activation with enhancement of the association between WSTF and PCAF while the association between WSTF and MOF was attenuated. The changes resulted in an increase of PCAF activity and decrease of MOF, and upregulation of H3K9ac and downregulation of H4K16ac followed by gene expression changes and enhancement of tumor formation. In conclusion, WSTF involved in regulation of PCAF and MOF, meanwhile, tumor formation was affected as a consequence of changes of H3K9ac, H4K16ac and tumor related gene expression.

breast cancer WSTF MOF PCAF

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit


[1]  Fournier J, Evans J P, Zappacosta F, et al. Acetylation of the Catalytic Lysine Inhibits Kinase Activity in PI3Kδ[J]. ACS Chemical Biology, 2021, 10(5): 12-17.
[2]  X An, Wei Z , Ran B , et al. Histone Deacetylase Inhibitor Trichostatin A Suppresses Cell Proliferation and Induces Apoptosis by Regulating the PI3K/AKT Signalling Pathway in Gastric Cancer Cells[J]. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents), 2020, 20(12): 106-116.
[3]  Liu Y, Wang D L, Chen S, et al. Oncogene Ras/Phosphatidylinositol 3-Kinase Signaling Targets Histone H3 Acetylation at Lysine 56[J]. Journal of Biological Chemistry, 2012, 287(49): 41469-41480.
[4]  Wijenayake S, Storey K B. Dynamic regulation of histone H3 lysine (K) acetylation and deacetylation during prolonged oxygen deprivation in a champion anaerobe[J]. Molecular and Cellular Biochemistry, 2020, 14(52): 51-67.
[5]  Nair V S , Saleh R , Toor S M , et al. Transcriptomic profiling disclosed the role of DNA methylation and histone modifications in tumor-infiltrating myeloid-derived suppressor cell subsets in colorectal cancer[J]. Clinical Epigenetics, 2020, 11(11): 37-40.
[6]  Mmab C, Jmpab C, Mdab C. Targeting histone modifications in cancer immunotherapy[J]. Histone Modifications in Therapy, 2020, 13(8): 373-394.
[7]  Kadam S, Bameta T, Padinhateeri R. Nucleosome sliding can influence the spreading of histone modifications[J]. 2021, 10(15): 73-87.
[8]  Khan A, Tomasi T B . Histone deacetylase regulation of immune gene expression in tumor cells[J]. Immunologic Research, 2008, 40(2): 164-178.
[9]  Edwards C M, Johnson R W. Targeting Histone Modifications in Bone and Lung Metastatic Cancers[J]. Current Osteoporosis Reports, 2021, 14(9): 1-17.
[10]  Huang R, Sui L, Fu C, et al. HDAC11 inhibition disrupts porcine oocyte meiosis via regulating α-tubulin acetylation and histone modifications[J]. Aging, 2021, 13(6): 45-57.
[11]  Sun L, Li Z, Ma Y, et al. PET Imaging of CD8 via SMART for Monitoring the Immunotherapy Response[J]. BioMed Research International, 2021, 10(5): 75-97.
[12]  Richter V A. Modification of a Tumor-Targeting Bacteriophage for Potential Diagnostic Applications[J]. Molecules, 2021, 26(20): 107-119.
[13]  Liu Y, Zhang Y Y, Wang S Q, et al. WSTF acetylation by MOF promotes WSTF activities and oncogenic functions[J]. Oncogene, 2020, 15(11): 67-79.
[14]  Lundqvist J, Kirkegaard T, Laenkholm A V, et al. Williams syndrome transcription factor (WSTF) acts as an activator of estrogen receptor signaling in breast cancer cells and the effect can be abrogated by 1α,25-dihydroxyvitamin D3.[J]. Journal of Steroid Biochemistry & Molecular Biology, 2017, 15(11): 67-79.
[15]  Cavellan E, Asp P, Percipalle P, et al. The WSTF-SNF2h chromatin remodeling complex interacts with several nuclear proteins in transcription.[J]. Journal of Biological Chemistry, 2006, 281(24): 16264-16271.
[16]  Legube, G. Tip60 is targeted to proteasome-mediated degradation by Mdm2 and accumulates after UV irradiation.[J]. Embo Journal, 2014, 21(7): 1704-1712.
[17]  Liu Y, Long Y, Xing Z, et al. C-Jun recruits the NSL complex to regulate its target gene expression by modulating H4K16 acetylation and promoting the release of the repressive NuRD complex[J]. Oncotarget, 2015, 6(16):14497-14506.
[18]  Liu Y, Xing Z, Wang S, et al. MDM2–MOF–H4K16ac axis contributes to tumorigenesis induced by Notch[J]. FEBS Journal, 2014, 281(5):144-156.
[19]  Yu-Feng L I, Liu Y, Yu-Hui L I, et al. H3K56ac Negatively Regulated by Ras-PI3K Pathway Promotes Proliferation and Invasion Abilities of MCF-7 Breast Cancer Cells[J]. Chinese Journal of Biochemistry and Molecular Biology, 2016, 156(34): 67-89.
[20]  Deng Y., Wang Y.Q., Li Y.C. et al., Mechanism study on migrationand proliferation of breast cancer induced with ras regulatedby H4K16ac, Genomics and Applied Biology) [J]. 2015, 34(11): 2306-2313
[21]  Zhang W, Huang J, Cook D E . Histone modification dynamics at H3K27 are associated with altered transcription of in planta induced genes in Magnaporthe oryzae[J]. PLoS Genetics, 2021, 17(2): 58-89.
[22]  Dx A, Hf A, Ji L A, et al. ChIP-seq assay revealed histone modification H3K9ac involved in heat shock response of the sea cucumber Apostichopus japonicus. 2022, 79(43):108-116.
[23]  Cardona F. Genome Profiling of H3k4me3 Histone Modification in Human Adipose Tissue during Obesity and Insulin Resistance[J]. Biomedicines, 2021, 9(7): 68-78.
[24]  Liu Y, Wang D L , Chang J F, et al. WSTF Phosphorylation Specifically Links H3K9ac with H4K16ac through PCAF/WSTF/MOF Complex[J]. Journal of Biological Chemistry, 2015:jbc.M114.627927.
[25]  Zippo A, Serafini R , Rocchigiani M, et al. Histone crosstalk between H3S10ph and H4K16ac generates a histone code that mediates transcription elongation. [J]. Cell, 2009, 138(6): 1122-1136.
[26]  Sugayama, SM Miuramoisés, Regina LúciaWag nfur, et al. Williams-Beuren syndrome: cardiovascular abnormalities in 20 patients diagnosed with fluorescence in situ hybridization[J]. Arquivos brasileiros de cardiologia, 2003, 81(5): 462-473.
[27]  Barnett C , Krebs J E . WSTF does it all: a multifunctional protein in transcription, repair, and replicationThis paper is one of a selection of papers published in a Special Issue entitled 31st Annual International Asilomar Chromatin and Chromosomes Conference, and has undergone[J]. Biochemistry and Cell Biology, 2011, 89(1): 12-23.