Bromodomain-containing protein

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Contents

Function

Bromodomain-containing proteins (BRD) are active as histone acetyltransferase, chromatin remodeling and transcriptional mediation. The bromodomain is a ca. 110 amino acid long sequence which recognizes acetylated lysine residues which are found in the C-terminal of histones[1].

  • BRD1 is essential for normal brain development[2].
  • BRD2 promotes spatial mixing and compartmentalisation of chromatin[3].
  • BRD3 and BRD4 regulate skeletal myogenesis[4]. For detalis on BRD3 see Human bromodomain containing protein 3
  • BRD7 promotes colorectal cancer by regulating the ubiquitin-proteasome-dependent stabilisation of c-Myc protein[5].
  • BRD9 has a role in activation of interferon-stimulated genes[6].

Disease

Dysfunction of BRD is involved in cancer, inflammation, obesity and multiple sclerosis[7]. BRD4 translocations are detected in NUT midline carcinoma and a variety of BRD4 inhibitors are clinically tested at the present[8].

Structural highlights

BRD4 bromodomain 1 inhibitors bind to the acetyl-binding pocket[9]. Water molecules are shown as red spheres.


3D Structures of bromodomain-containing protein

Bromodomain-containing protein 3D structures


Human bromodomain-containing protein 4 bromodomain 1 complex with inhibitor and ethylene glycol (PDB code 3p5o)

Drag the structure with the mouse to rotate

References

  1. ↑ Zeng L, Zhou MM. Bromodomain: an acetyl-lysine binding domain. FEBS Lett. 2002 Feb 20;513(1):124-8. PMID:11911891
  2. ↑ Paternoster V, Cömert C, Kirk LS, la Cour SH, Fryland T, Fernandez-Guerra P, Stougaard M, Nyengaard JR, Qvist P, Bross P, Børglum AD, Christensen JH. The psychiatric risk gene BRD1 modulates mitochondrial bioenergetics by transcriptional regulation. Transl Psychiatry. 2022 Aug 8;12(1):319. PMID:35941107 doi:10.1038/s41398-022-02053-2
  3. ↑ Xie L, Dong P, Qi Y, Hsieh TS, English BP, Jung S, Chen X, De Marzio M, Casellas R, Chang HY, Zhang B, Tjian R, Liu Z. BRD2 compartmentalizes the accessible genome. Nat Genet. 2022 Apr;54(4):481-491. PMID:35410381 doi:10.1038/s41588-022-01044-9
  4. ↑ Roberts TC, Etxaniz U, Dall'Agnese A, Wu SY, Chiang CM, Brennan PE, Wood MJA, Puri PL. BRD3 and BRD4 BET Bromodomain Proteins Differentially Regulate Skeletal Myogenesis. Sci Rep. 2017 Jul 21;7(1):6153. PMID:28733670 doi:10.1038/s41598-017-06483-7
  5. ↑ Zhao R, Liu Y, Wu C, Li M, Wei Y, Niu W, Yang J, Fan S, Xie Y, Li H, Wang W, Zeng Z, Xiong W, Li X, Li G, Zhou M. BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer. Front Cell Dev Biol. 2021 May 24;9:659392. PMID:34109174 doi:10.3389/fcell.2021.659392
  6. ↑ Ahmed NS, Gatchalian J, Ho J, Burns MJ, Hah N, Wei Z, Downes M, Evans RM, Hargreaves DC. BRD9 regulates interferon-stimulated genes during macrophage activation via cooperation with BET protein BRD4. Proc Natl Acad Sci U S A. 2022 Jan 4;119(1):e2110812119. PMID:34983841 doi:10.1073/pnas.2110812119
  7. ↑ Belkina AC, Denis GV. BET domain co-regulators in obesity, inflammation and cancer. Nat Rev Cancer. 2012 Jun 22;12(7):465-77. doi: 10.1038/nrc3256. PMID:22722403 doi:http://dx.doi.org/10.1038/nrc3256
  8. ↑ French CA. Demystified molecular pathology of NUT midline carcinomas. J Clin Pathol. 2010 Jun;63(6):492-6. doi: 10.1136/jcp.2007.052902. Epub 2008 Jun , 13. PMID:18552174 doi:http://dx.doi.org/10.1136/jcp.2007.052902
  9. ↑ French CA. Demystified molecular pathology of NUT midline carcinomas. J Clin Pathol. 2010 Jun;63(6):492-6. doi: 10.1136/jcp.2007.052902. Epub 2008 Jun , 13. PMID:18552174 doi:http://dx.doi.org/10.1136/jcp.2007.052902

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