Secondary literature sources for the PHD domain

For each of the hand selected primary papers associated with the PHD domain, 100 neighbouring papers are retrieved from PubMed. If one of these neighbouring papers is referenced by more than two primary papers, it is shown in the table below.

The chromatin remodeling complex NoRC targets HDAC1 to the ribosomal gene promoter and represses RNA polymerase I transcription.

Zhou Y, Santoro R, Grummt I
EMBO J. 2002; 21: 4632-40

Mammalian chromatin remodeling complexes are involved in both activation and repression of transcription. Here, we show that NoRC, a SNF2h- containing nucleolar chromatin remodeling complex, represses ribosomal gene transcription. NoRC-mediated rDNA silencing was alleviated by trichostatin A, indicating that histone deacetylation is causally involved in silencing. Chromatin immunoprecipitation experiments demonstrate that overexpression of TIP5, the large subunit of NoRC, mediates deacetylation of nucleosomes in the vicinity of the rDNA promoter. Protein-protein interaction assays reveal association of TIP5 with the histone deacetylase HDAC1 in vivo and in vitro. Deletion of the C-terminal PHD finger and bromodomain abolishes the interaction of TIP5 and HDAC1, and abrogates transcriptional repression. The results suggest that NoRC silences the rDNA locus by targeting the SIN3 corepressor complex to the rDNA promoter, thereby establishing a repressed chromatin structure.

Pf1, a novel PHD zinc finger protein that links the TLE corepressor to the mSin3A-histone deacetylase complex.

Yochum GS, Ayer DE
Mol Cell Biol. 2001; 21: 4110-8

The mSin3A-histone deacetylase corepressor is a multiprotein complex that is recruited by DNA binding transcriptional repressors. Sin3 has four paired amphipathic alpha helices (PAH1 to -4) that are protein-protein interaction motifs and is the scaffold upon which the complex assembles. We identified a novel mSin3A-interacting protein that has two plant homeodomain (PHD) zinc fingers we term Pf1, for PHD factor one. Pf1 associates with mSin3A in vivo and recruits the mSin3A complex to repress transcription when fused to the DNA binding domain of Gal4. Pf1 interacts with Sin3 through two independent Sin3 interaction domains (SIDs), Pf1SID1 and Pf1SID2. Pf1SID1 binds PAH2, while Pf1SID2 binds PAH1. Pf1SID1 has sequence and structural similarity to the well-characterized 13-amino-acid SID of the Mad bHLHZip repressor. Pf1SID2 does not have sequence similarity with either Mad SID or Pf1SID1 and therefore represents a novel Sin3 binding domain. Mutations in a minimal fragment of Pf1 that encompasses Pf1SID1 inhibited mSin3A binding yet only slightly impaired repression when targeted to DNA, implying that Pf1 might interact with other corepressors. We show that Pf1 interacts with a mammalian homolog of the Drosophila Groucho corepressor, transducin-like enhancer (TLE). Pf1 binds TLE in an mSin3A-independent manner and recruits functional TLE complexes to repress transcription. These findings suggest that Pf1 may serve to bridge two global transcription networks, mSin3A and TLE.

Fusion protein of retinoic acid receptor alpha with promyelocytic leukemia protein or promyelocytic leukemia zinc finger protein recruits N-CoR-TBLR1 corepressor complex to repress transcription in vivo.

Tomita A, Buchholz DR, Obata K, Shi YB
J Biol Chem. 2003; 278: 30788-95

Fusion proteins of retinoic acid receptor alpha (RARalpha) with promyelocytic leukemia protein (PML-RARalpha) or with promyelocytic leukemia zinc finger protein (PLZF-RARalpha) are associated with and likely responsible for the development of acute promyelocytic leukemia. These oncoproteins retain the ability to bind DNA and retinoic acid through the RARalpha moiety. This enables them to repress RARalpha target genes in the absence of retinoic acid, but the underlying mechanisms remain to be investigated. Here we use the frog oocyte system to study transcriptional regulation by PML-RARalpha and PLZF-RARalpha in the context of chromatin. We first show that the endogenous corepressor N-CoR forms a complex with TBLR1 (transducin beta-like protein 1-related protein) and that both N-CoR and TBLR1 can interact with unliganded PML-RARalpha and PLZF-RARalpha in vivo. Using chromatin immunoprecipitation, we demonstrate that both oncoproteins recruit TBLR1, as well as N-CoR, to its target promoter, leading to histone deacetylation and transcriptional repression. Furthermore, expression of a dominant negative N-CoR that contains the TBLR1-interacting domain blocks transcription repression by unliganded PML-RARalpha and PLZF-RARalpha. Thus, our studies provide in vivo evidence for targeted recruitment of N-CoR-TBLR1 complexes by PML-RARalpha and PLZF-RARalpha in transcriptional repression in the context of chromatin.

J. Lawrence Oncley, PhD Biophysicist February 14, 1910-July 14, 2004.

Thyng NA, August LO
Biophys Chem. 2005; 113: 103-103

The KRAB domain of zinc finger gene ZNF268: a potential transcriptional repressor.

Sun Y, Gou DM, Liu H, Peng X, Li WX
IUBMB Life. 2003; 55: 127-31

Nearly one-third of Krupple-type C2H2 zinc finger proteins have a krupple-associated box (KRAB) domain, which may act as a transcriptional repressor. ZNF268, which was novelty isolated from early human embryo, is a typical krupple-type C2H2 zinc finger protein with a conserved KRAB domain. In this report, the KRAB domain of ZNF268 is identified to localize in the nucleus and has transcriptional repressor activity.

Mi-2 beta associates with BRG1 and RET finger protein at the distinct regions with transcriptional activating and repressing abilities.

Shimono Y, Murakami H, Kawai K, Wade PA, Shimokata K, Takahashi M
J Biol Chem. 2003; 278: 51638-45

Mi-2 beta is the main component of the nucleosome remodeling and deacetylase complex and plays an important role in epigenetic transcriptional repression. Here we show that the amino-terminal and carboxyl-terminal regions of Mi-2 beta have distinct transcriptional activities and bind to BRG1, a component of the SWI/SNF complex, and the RET finger protein (RFP), respectively. Analysis by luciferase reporter assay revealed that the amino-terminal region of Mi-2 beta has a strong transactivating ability, whereas its carboxyl-terminal region has transcriptional repressive activity. Co-localization and association of Mi-2, RFP, and histone deacetylase 1 suggested that these proteins cooperate in transcriptional repression. Furthermore, the functional importance of the association of Mi-2 beta and RFP was confirmed by using Rfp-/- fibroblasts. On the other hand, we demonstrated that Mi-2 and BRG1 were associated with each other and that the bromodomain region of BRG1 strongly suppressed transactivation by the amino-terminal region of Mi-2 beta. The findings that Mi-2 beta interacts with both transactivating and repressing proteins and directly associates with another chromatin remodeling protein, BRG1, provide new insight into the formation of multiprotein supercomplex involved in transcriptional regulation.

Polycomblike PHD fingers mediate conserved interaction with enhancer of zeste protein.

O'Connell S, Wang L, Robert S, Jones CA, Saint R, Jones RS
J Biol Chem. 2001; 276: 43065-73

The products of Polycomb group (PcG) genes are required for the epigenetic repression of a number of important developmental regulatory genes, including homeotic genes. Enhancer of zeste (E(Z)) is a Drosophila PcG protein that previously has been shown to bind directly to another PcG protein, Extra Sex Combs (ESC), and is present along with ESC in a 600-kDa complex in Drosophila embryos. Using yeast two-hybrid and in vitro binding assays, we show that E(Z) binds directly to another PcG protein, Polycomblike (PCL). PCL.E(Z) interaction is shown to be mediated by the plant homeodomain (PHD) fingers domain of PCL, providing evidence that this motif can act as an independent protein interaction domain. An association was also observed between PHF1 and EZH2, human homologs of PCL and E(Z), respectively, demonstrating the evolutionary conservation of this interaction. E(Z) was found to not interact with the PHD domains of three Drosophila trithorax group (trxG) proteins, which function to maintain the transcriptional activity of homeotic genes, providing evidence for the specificity of the interaction of E(Z) with the PCL PHD domain. Coimmunoprecipitation and gel filtration experiments demonstrate in vivo association of PCL with E(Z) and ESC in Drosophila embryos. We discuss the implications of PCL association with ESC.E(Z) complexes and the possibility that PCL may either be a subunit of a subset of ESC.E(Z) complexes or a subunit of a separate complex that interacts with ESC.E(Z) complexes.

Allen A. Rovick, PhD: in memoriam.

Michael J
Adv Physiol Educ. 2005; 29: 58-58

In remembrance: Hanno Boon, PhD (1970-2004).

Meiring JH
Clin Anat. 2005; 18: 224-225

No abstract.

The PHD type zinc finger is an integral part of the CBP acetyltransferase domain.

Kalkhoven E, Teunissen H, Houweling A, Verrijzer CP, Zantema A
Mol Cell Biol. 2002; 22: 1961-70

Histone acetyltransferases (HATs) such as CBP and p300 are regarded as key regulators of RNA polymerase II-mediated transcription, but the critical structural features of their HAT modules remain ill defined. The HAT domains of CBP and p300 are characterized by the presence of a highly conserved putative plant homeodomain (PHD) (C4HC3) type zinc finger, which is part of the functionally uncharacterized cysteine-histidine-rich region 2 (CH2). Here we show that this region conforms to the PHD type zinc finger consensus and that it is essential for in vitro acetylation of core histones and the basal transcription factor TFIIE34 as well as for CBP autoacetylation. PHD finger mutations also reduced the transcriptional activity of the full-length CBP protein when tested on transfected reporter genes. Importantly, similar results were obtained on integrated reporters, which reflect a more natural chromatinized state. Taken together, our results indicate that the PHD finger forms an integral part of the enzymatic core of the HAT domain of CBP.

Must they have a PhD?

Johnson M
Nurse Educ Today. 2000; 20: 511-2

Literature reviewed by Donna Hallas, PhD, APRN, BC, CPNP.

Hallas D
J Pediatr Health Care. 2005; 19: 190-1

Lemuel J. Bowie, PhD (1944-1998)

Gochman N
Clin Chem. 1999; 45: 590-590

Janice M. Pfeffer, PhD

Frohlich ED
Hypertension. 2000; 36: 1-1

Laird wilson, jr, PhD. (1943-2000)

Fazleabas AT
J Soc Gynecol Investig. 2000; 7: 203-4

Solution structure of the PHD domain from the KAP-1 corepressor: structural determinants for PHD, RING and LIM zinc-binding domains.

Capili AD, Schultz DC, RauscherIII FJ, Borden KL
EMBO J. 2001; 20: 165-77

Plant homeodomain (PHD) domains are found in >400 eukaryotic proteins, many of which are transcriptional regulators. Naturally occurring point mutations or deletions of this domain contribute to a variety of human diseases, including ATRX syndrome, myeloid leukemias and autoimmune dysfunction. Here we report the first structural characterization of a PHD domain. Our studies reveal that the PHD domain from KAP-1 corepressor binds zinc in a cross-brace topology between anti-parallel ss-strands reminiscent of RING (really interesting new gene) domains. Using a mutational analysis, we define the structural features required for transcriptional repression by KAP-1 and explain naturally occurring, disease-causing mutations in PHD domains of other proteins. From a comparison of this PHD structure with previously reported RING and LIM (Lin11/Isl-1/Mec-3) structures, we infer sequence determinants that allow discrimination among PHD, RING and LIM motifs.