Löytyi artikkeli ZBTB-proteiinien ryhmästä: 49 kappaletta.

doi: 10.1007/s12185-016-2035-x

• Review Article
• Published: 01 June 2016

 Suomennosta: Hematopoieettinen kehitys (verisolujen kehittyminen omia linjojaan) säätyy ZBTB- transkriptiotekijöillä.  Eri solu injaspesifiset geenit ja  eri erilaistumisvaiheiden  geenit ilmentyvät koordinoidusti  johtamaan hematopoieettista kehitystä.  Transkriptiotekijöillä on tässä päätehtäviään ja jos niissä on hämminkiä, se ilmenee  erilaisina hematologisina ja immunologisina häiriöinä. Ihmisen  genomista  koodautuu  lähes  1900 transkriptiofaktoria. Niistä on  BTB-domaanin omaavia sinkkisormiproteiineja  49 kappaletta. ( BTB on lythennys englantilaisista  sanoista Broad-complex, Tram-track and Bric a´ brac. Ne ovat nimiä,  joita on annettu  ensimmäisille  geeni-homologeille  ehkä  banaanikärpäsellä tai muulla  tieteen  tarkasti tutkimalla  eliöllä ja sitten on vastaavaa geeniä löytynyt ihmiskunnasta ja näin  geenidomeeninb nimi siirtyy ihmisen geenin osien nimiin jonain käytännöllisenä lyhennyksenä, jolla  geenejä voi  tieteen kirjallisuudessa ryhmittää ja  erottaa  toisistaan). ZBTB-proteiineilla on myös toinen nimi POK- proteiini. BTB domeenia sanotaan myös POZ- domeeniksi, mikä  tulee sanoista  " poxvirus and zinc finger".  Sinkkisormi struktuurilla on oma tyyppinsä näissäkin.    Lisäksi molekyylillä on Krüppel-tyyppisiä  sinkkisormia, mistä  K- kirjain.  (C- terminaaliset  sinkkisormet näyttävät  duaalirakenteisilta näissä proteiineissa PubMed sekvensseissä). 

Regulation of hematopoietic development by ZBTB transcription factors

• Takahiro Maeda 

International Journal of Hematology volume 104, pages310–323(2016)Cite this article

Abstract

Hematopoietic development is governed by the coordinated expression of lineage- and differentiation stage-specific genes. Transcription factors play major roles in this process and their perturbation may underlie hematologic and immunologic disorders. Nearly 1900 transcription factors are encoded in the human genome: of these, 49 BTB (for broad-complex, tram-track and bric à brac)-zinc finger transcription factors referred to as ZBTB or POK proteins have been identified. ZBTB proteins, including BCL6, PLZF, ThPOK and LRF, exhibit a broad spectrum of functions in normal and malignant hematopoiesis. This review summarizes developmental and molecular functions of ZBTB proteins relevant to hematology.

ZBTB protein molecular mechanisms

ZBTB proteins are prototypical TFs consisting of an N-terminal BTB domain functioning in protein–protein interactions and C-terminal C2H2/Krüppel-type zinc fingers, which bind DNA (Fig. 1a). Between those domains lies a linker domain, whose amino acid sequence is less conserved among family proteins (Fig. 1a). The BTB domain was named after three Drosophila genes, broad-complex, tram-track and bric à brac, all encoding proteins essential for Drosophila development [12]. The BTB domain is also known as the POZ (for poxvirus and zinc finger) domain, as it is present in many poxvirus-related proteins [13]; thus ZBTB proteins are sometimes referred as POK (POZ and krüppel-type zinc fingers) proteins.

The BTB domain

The BTB domain exerts two major functions: dimer formation and recruitment of transcriptional regulators (Fig. 1a). Biochemical and structural analyses revealed that the domain forms an obligate homodimer [7], which is essential for ZBTB protein function in some contexts

ZBTB7A:

  For example, wild-type LRF [for Leukemia/lymphoma-Related Factor [14] (also known as FBI-1 [15], POKE-MON [16], OCZF [17]); encoded by ZBTB7A] can rescue germinal center B cell defects observed in Lrf conditional knockout (KO) mice, while a dimerization-deficient LRF mutant cannot [18]. 

 ZBTB27:

 The BTB domain can also mediate heterodimer formation. Among heterodimers identified are LRF and BCL6 (B cell Lymphoma 6; encoded by ZBTB27) 

ZBTB17:

[14], BCL6 and MIZ-1 (Myc-interacting zinc finger protein-1; encoded by ZBTB17) [19],

ZBTB28:

BCL6 and BCL6B (a.k.a. BAZF; encoded by ZBTB28) [20] and 

ZBTB16:

PLZF (Promyelocytic Leukemia Zinc Finger; encoded by ZBTB16) and

 ZBTB32;

 FAZF (also known as ROG [21], PLZP [22], or TZFP [23]; encoded by ZBTB32). 

 It remains unclear whether only BTB domains mediate heteromeric interactions. Higher order oligomerization through the BTB domain has also been reported: PLZF-BTB domain can form oligomers through its N-terminal β-sheet [24], whereas the MIZ-1 BTB domain forms a tetramer [25].

BTB domains can also recruit transcriptional regulators (Fig. 1a). The transcriptional co-repressors NCOR (nuclear receptor co-repressor) and SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) are homologous proteins originally identified as co-repressors for retinoic acid receptors (RARs) and thyroid hormone receptors [26, 27]. These co-repressors function via recruiting histone deacetylases (HDACs), namely HDAC3 [28]. The functional connection between BTB domains and co-repressors became apparent when NCOR and SMRT were identified in a complex with the leukemia-associated RAR fusion proteins, PML-RARα and PLZF-RARα [29–31]. The latter interacts with SMRT/NCOR not only through the C-terminal RAR moiety but also through the N-terminal PLZF-BTB domain [29, 32, 33]. The BCL6 BTB domain was subsequently found to associate with both SMRT and NCOR [34, 35]. Importantly, BTB homodimer formation is a prerequisite to co-repressor recruitment [36]. Structural analysis revealed that a 17 amino acid residue of SMRT, called SMRT-BBD (SMRT-BCL6 binding domain), binds to a surface created by a BTB homodimer [36]. Thus, any potential BCL6 monomer cannot recruit the co-repressor complex. A recent study suggested that BCL6 serves as a critical downstream effector of SMRT/NCOR [37]. ChIP-seq (chromatin immunoprecipitation with massively parallel DNA sequencing) analysis revealed that nearly half of SMRT/NCOR binding sites were reduced or lost in Bcl6 KO macrophages [37]. Furthermore, almost 70 % of DNA occupancy sites are shared between SMRT-BCL6 and NCOR-BCL6 complexes, indicating a high degree of overlap between both co-repressors in the context of BCL6-mediated gene silencing [37]....