CR Name:
Species:    Tissue or Cell: 

Chromatin Regulator

Alias

BRD4HUNK1;MCAP;CAP

External Links:

Wiki    GeneCards    NCBI    UniProt

Related histone modifications:

H3K14ac;H3K122ac;H4K5ac;H4K12ac

Introduction

Full name: Bromodomain Containing 4. BRD4 is a member of the BET family that in yeast and animals contains two tandem bromodomains(BDI and BDII) and an extraterminal (ET) domain,is a chromatin binding factor with preference for acetylated Lys-14 on histone H3 and Lys-5/12 on H4.BRD4 is essential for cellular growth and has been implicated in cell cycle control,DNA replication and gene rearrangement(1-3).

Function and Interaction

BRD4 localizes to the condensed chromosomes during mitosis,interacts with the euchromatic regions of chromosomes,play an important reole in cell cycle progression to mitosis(4).Brd4 has been found in several transcription complexes,including the general cofactor Mediator and the P-TEFb elongation factor(3,5,6).Brd4 is a component of transcriptional silencing complex assembled by HPV E2 and turns out to be the long sought cellular corepressor that inhibits the expression of HPV-encoded E6 and E7 oncoproteins that antagonize p53 and pRB tumor supressor activity,respectively(3,7).BRD4 is an atypical protein kinase which directly and specifically phosphorylates the RNA polymerase II (Pol II) CTD (the carboxyl-terminal domain) at the Ser2 position to regulate transcription(8).

Disease Association

BRD4 is associated with nuclear protein in testis (NUT) midline carcinomas, NUT is involved in a balanced translocation with the BRD4 gene on chromosome 19p13.1(9).

ChIP-Seq data


SpeciesCell lineCell typeTissueDataDownloadSend to CistromeAnalysis FiguresComparisonReference
Mus musculusNIH-3T3FibroblastEmbryoGSE58731 ,GSM1418770
Click  DownloadNA25383670

ChIP-Seq data of related histone modifications


Products/SubstratesSpeciesCell lineCell typeTissueDataDownload Send to CistromeAnalysis FiguresReference
H3K122ac Homo sapiens MCF-7 Epithelium Mammary Gland GSE35954 ,GSM1059385 Bed     Big wiggle
Click   Download23415232
H3K14ac Homo sapiens MCF-7 Epithelium Mammary Gland GSE23701 ,GSM588574 Bed     Big wiggle
Click   Download21179027
H3K14ac Homo sapiens MCF-7 Epithelium Mammary Gland GSE23701 ,GSM588575 Bed     Big wiggle
Click   Download21179027
H4K5ac Homo sapiens H1 Embryonic Stem Cell Embryo GSE16256 ,GSM605330 Bed     Big wiggle
Click   Download19829295
H4K5ac Homo sapiens H9 Embryonic Stem Cell Embryo GSE16256 ,GSM667635 Bed     Big wiggle
Click   Download19829295
H4K5ac Homo sapiens H9 Embryonic Stem Cell Embryo GSE16256 ,GSM667636 Bed     Big wiggle
Click   Download19829295
H3K14ac Homo sapiens H9 Embryonic Stem Cell Embryo GSE16256 ,GSM752964 Bed     Big wiggle
Click   Download19829295
H3K14ac Homo sapiens H1 Embryonic Stem Cell Embryo GSE16256 ,GSM818021 Bed     Big wiggle
Click   Download19829295
H3K14ac Homo sapiens H9 Embryonic Stem Cell Embryo GSE16256 ,GSM896161 Bed     Big wiggle
Click   Download19829295
H3K14ac Homo sapiens H1 Embryonic Stem Cell Embryo GSE16256 ,GSM908945 Bed     Big wiggle
Click   Download19829295
H3K14ac Homo sapiens H1 Embryonic Stem Cell Embryo GSE16256 ,GSM908946 Bed     Big wiggle
Click   Download19829295
H4K12ac Homo sapiens H1 Embryonic Stem Cell Embryo GSE16256 ,GSM908962 Bed     Big wiggle
Click   Download19829295
H4K12ac Homo sapiens H1 Embryonic Stem Cell Embryo GSE16256 ,GSM908963 Bed     Big wiggle
Click   Download19829295

Notice: For bigwiggle or bed file download, if the browser cannot automatically download the file, users can right click the hyperlink and then click the "Save link as..." button, which will automatically redirect to download dialogue box, or click the "Copy link address" button and access the website in a new tab page. For data analysis in Cistrome, users should first login into the Cistrome website, then press the "Send Bed" or "Send Big wiggle" button. For data download by Cistrome, users can follow this tutorial.

References

1.Florence, B., and Faller, D.V. (2001). You bet-cha:a novel family of transcriptional regulators. Front Biosci 6, D1008–1018.
2.Dey, A., Chitsaz, F., Abbasi, A., Misteli, T., and Ozato, K. (2003). The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis. Proc Natl Acad Sci U S A 100, 8758-8763.
3.Wu, S.Y., and Chiang, C.M. (2007). The double bromodomain-containing chromatin adaptor Brd4 and transcriptional regulation. J Biol Chem 282, 13141-13145.
4.Dey, A., Ellenberg, J., Farina, A., Coleman, A.E., Maruyama, T., Sciortino, S., Lippincott-Schwartz, J., and Ozato, K. (2000). A bromodomain protein, MCAP, associates with mitotic chromosomes and affects G(2)-to-M transition. Mol Cell Biol 20, 6537-6549.
5.Jiang, Y.W., Veschambre, P., Erdjument-Bromage, H., Tempst, P., Conaway, J.W., Conaway, R.C., and Kornberg, R.D. (1998). Mammalian mediator of transcriptional regulation and its possible role as an end-point of signal transduction pathways. Proc Natl Acad Sci U S A 95, 8538-8543.
6.Yang, Z., Yik, J.H., Chen, R., He, N., Jang, M.K., Ozato, K., and Zhou, Q. (2005). Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Mol Cell 19, 535-545.
7.Wu, S.Y., Lee, A.Y., Hou, S.Y., Kemper, J.K., Erdjument-Bromage, H., Tempst, P., and Chiang, C.M. (2006). Brd4 links chromatin targeting to HPV transcriptional silencing. Genes Dev 20, 2383-2396.
8.Devaiah, B.N., Lewis, B.A., Cherman, N., Hewitt, M.C., Albrecht, B.K., Robey, P.G., Ozato, K., Sims, R.J., 3rd, and Singer, D.S. (2012). BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc Natl Acad Sci U S A 109, 6927-6932.
9.French, C.A. (2010). Demystified molecular pathology of NUT midline carcinomas. J Clin Pathol 63, 492-496.

Figure Gallery

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About Chromatin Regulator

Chromatin Regulator Cistrome
is a unique database integrating curated information of CRs, CR ChIP-seq datasets, CR related HM ChIP-seq datasets, and analysis of the relationship between CRs and HMs ChIP-seq pairs in human and mouse.