Peregrin also known as bromodomain and PHD finger-containing protein 1 is a protein that in humans is encoded by the BRPF1 gene located on 3p26-p25. Peregrin is a multivalent chromatin regulator that recognizes different epigenetic marks and activates three histone acetyltransferases (Moz, Morf and Hbo1). BRPF1 contains two PHD fingers, one bromodomain and one chromo/Tudor-related Pro-Trp-Trp-Pro (PWWP) domain.
File:模式图1-01-01.tifBrpf1 forms a stable complex with Moz/Morf-Hbo1 and targets to chromatin to regulate transcription.[1]File:Brpf1 name.tifBrpf1 null mutant mouse dies at embryonic day 9.5.[2][3] Forebrain-specific knock out of Brpf1 cause hypoplasia in the dentate gyrus of mouse.[4]
Embryo development
Brpf1 gene is very conserved and has a critical role in different developmental processes.[1][2][3]Zebrafish BRPF1, which is coordinated by its particular set of PWWP domains, mediates Moz -dependent histone acetylation and maintains Hox genes expression throughout vertebrate development, hence determines the proper pharyngeal segmental identities.[5] Furthermore, Brpf1 may not only has significant role for maintaining the anterior-posterior axis of the craniofacial skeleton, but also the dorsal-ventral axis of the caudal skeleton.[6] Recent studies have shown that ablation of the mouse Brpf1 gene causes embryonic lethality at embryonic day 9.5.[2][3] Specifically, Brpf1 regulates placenta vascular formation, neural tube closure, primitive hematopoiesis and embryonic fibroblast proliferation.[2][3]
Recently, Brpf1 was reported to play the tumor suppressor or oncogenic role in several malignant tumors, including leukemia, medulloblastoma and endometrial stromal sarcoma.[1][8][9][10]Brpf1 was considered a tumor suppressor gene because mutations in cancer cells appear to diminish the function of Brpf1[8][9] However, oncogenic role of Brpf1 is also possible in cancer. For example, Brpf1 can form a stable complex with Moz-Tif2, which could lead to the development of human acute myeloid leukemia (AML).[10] There is another Brpf1 related complex Brpf1–Ing5–Eaf6, which also plays a direct role in cancer.[1]
↑ 1.01.11.21.3Yang XJ (2015). "MOZ and MORF acetyltransferases: Molecular interaction, animal development and human disease". Biochimica et Biophysica Acta. 1853 (8): 1818–26. doi:10.1016/j.bbamcr.2015.04.014. PMID25920810.
↑Hibiya K, Katsumoto T, Kondo T, Kitabayashi I, Kudo A (2009). "Brpf1, a subunit of the MOZ histone acetyl transferase complex, maintains expression of anterior and posterior Hox genes for proper patterning of craniofacial and caudal skeletons". Developmental Biology. 329 (2): 176–90. doi:10.1016/j.ydbio.2009.02.021. PMID19254709.
↑ 10.010.1Shima H, Yamagata K, Aikawa Y, Shino M, Koseki H, Shimada H, Kitabayashi I (2014). "Bromodomain-PHD finger protein 1 is critical for leukemogenesis associated with MOZ-TIF2 fusion". International Journal of Hematology. 99 (1): 21–31. doi:10.1007/s12185-013-1466-x. PMID24258712.
Mishima Y, Miyagi S, Saraya A, Negishi M, Endoh M, Endo TA, Toyoda T, Shinga J, Katsumoto T, Chiba T, Yamaguchi N, Kitabayashi I, Koseki H, Iwama A (Sep 2011). "The Hbo1-Brd1/Brpf2 complex is responsible for global acetylation of H3K14 and required for fetal liver erythropoiesis". Blood. 118 (9): 2443–53. doi:10.1182/blood-2011-01-331892. PMID21753189.
Vezzoli A, Bonadies N, Allen MD, Freund SM, Santiveri CM, Kvinlaug BT, Huntly BJ, Göttgens B, Bycroft M (May 2010). "Molecular basis of histone H3K36me3 recognition by the PWWP domain of Brpf1". Nature Structural & Molecular Biology. 17 (5): 617–9. doi:10.1038/nsmb.1797. PMID20400950.
Hibiya K, Katsumoto T, Kondo T, Kitabayashi I, Kudo A (May 2009). "Brpf1, a subunit of the MOZ histone acetyl transferase complex, maintains expression of anterior and posterior Hox genes for proper patterning of craniofacial and caudal skeletons". Developmental Biology. 329 (2): 176–90. doi:10.1016/j.ydbio.2009.02.021. PMID19254709.