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“Of particular interesf’ - in the opinion of geneticists and developmental biologists. Authors of reviews in the Current Opinion series of journals select from the previous year’s papers those they consider to be “of particular interest”. They justify each selection in a short ‘annotation’. Some of the selected references from the April 1992 issue of Current Opinion in Genetics and Development, which covers both Gene Expression and Differentiation, are listed below under the titles of the reviews. The inhibitory ankyrin and activator Rel proteins by Carry P. Nolan and David Baltimore HASKILL S, BEG AA, TOMPKINS SM, Mom JS, YUROCHKO AD, A, MONDAL K, RALPH P, BALDWIN AS: Characterization of an Immediate Early Gene In- duced in Adherant Monocytes that Encodes IxB-like Activity. Cell 1991, 651281-1289. An important paper detailing the cloning of an IxB. De- fines a potential functional similarity of the ankyrin do- mains in IxB and the ~105 precursor. Suggests a role for ankyrin domains in protein IxB-NF-xB interactions. LU D, ?-HOMFSON JD, GORSKI GK, RICE NR, h'kYER MG, YUNIS JJ: Alterations at the c-rel Locus in Human Lymphoma Oncogene 1991, 6:1235-1241. Alterations in c-rel are shown to be involved in human B- cell malignancy. Interestingly, several of the tumours stud- ied have additional translocations involving other onco- genes, suggesting that c-ref mutations are but one step in a process of Rel-induced leukaemogenesis. Structure of the leucine zipper by Tom Alber O’SHEA EK, KLEMM JD, KIM PS, ALBER T: X-ray Struc- ture of the GCN4 Leucine Zipper, a Two-stranded, ParaIIel Coiled Coil. Science l%l, 254~539-544. The first high resolution X-ray cfystal structure of a leucine zipper. The diagrams in this work illustrate im- portant structural features. O’SHEA EK, RUTKOWSKI R, KIM PS: Mechanism of Speci- ficity in the Fos-Jun Oncoprotein Dimer. Cell 192, 68:699-708. Extensive physical analysis of hybrid leucine-zipper pep- tides shows that electrostatic complementarity stabi- lizes the Fos-Jun heterodimer and anti-complementarity destabilizes the Fos homodimer. Volume 2 Number 5 1992 Mechanisms of liver-specific gene expression by Frances M. Sladek and James E. Darnell CHRISTY RJ, KAESTNER KH, GEIMAN DE, LANE MD: CCAAT/Enhancer Binding Protein Gene Promoter: Binding of Nuclear Factors During Differentiation of 3T3-Ll Pre-adipocytes. Proc Nat1 Acad Sci LISA 1991, 88:2593-2597. The first work analyzing the promoter of a liver-enriched transcription factor. The authors lind that C/EBPy is regu- lated not only by a factor present in undifferentiated cells (preadipocytes) but also by a C/EBP-like factor. This re- sult suggests the occurrence of autoregulation. bbWDEL DB, KHAVARI PA, CONIEY PB, GRAVES MIS, HANSEN IP, ADMON A, CRABTREE GR Characteriza- tion of a Cofactor that Regulates Dimerkation of a Mammalian Homeodomain Protein. Science 1931, 254:1762-1767. Presents the first evidence indicating that a non-DNA- binding protein (DCoH) might play a role in tissue-re- stricted gene expression. Unlike other such factors (also termed adapters, co-activators or bridging proteins) that have recently been described, this co-factor does not ap- pear to interact with the basal transcription machinery. Rather, it appears to function by stabilizing HNF-101 (and HNF-10) homodimers. Myb: a transcriptional activator linking proliferation and differentiation in hematopoietic cells by Thomas Graf MUCENSKI ML, McLm K, KIER AB, SW-ERDLOW SH, SCHREINER CM, MILLER TA, PIETRYGA DW, Scorn, WJ, POITER SS: A Functional c-myb Gene is Required for Normal Murine Fetal Hepatic Hematopoiesis. Cell 1991, 65:6n-689. In this work, c-m@ is inactivated in embryonic stem cells by homologous recombination, and transgenic mice homozygous for the alteration are obtained by breed- ing. The mice develop a severe anemia at approxi- 265

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Page 1: Myb: a transcriptional activator linking proliferation and differentiation in hematopoietic cells

“Of particular interesf’ - in the opinion of geneticists and developmental biologists.

Authors of reviews in the Current Opinion series of journals select from the previous year’s papers those they consider to be “of particular interest”. They justify each selection in a short ‘annotation’. Some of the selected references from the April 1992 issue of Current Opinion in Genetics and Development, which covers both

Gene Expression and Differentiation, are listed below under the titles of the reviews.

The inhibitory ankyrin and activator Rel proteins by Carry P. Nolan and David Baltimore

HASKILL S, BEG AA, TOMPKINS SM, Mom JS, YUROCHKO AD, A, MONDAL K, RALPH P, BALDWIN AS: Characterization of an Immediate Early Gene In- duced in Adherant Monocytes that Encodes IxB-like Activity. Cell 1991, 651281-1289.

An important paper detailing the cloning of an IxB. De- fines a potential functional similarity of the ankyrin do- mains in IxB and the ~105 precursor. Suggests a role for ankyrin domains in protein IxB-NF-xB interactions.

LU D, ?-HOMFSON JD, GORSKI GK, RICE NR, h'kYER MG, YUNIS JJ: Alterations at the c-rel Locus in Human Lymphoma Oncogene 1991, 6:1235-1241.

Alterations in c- rel are shown to be involved in human B- cell malignancy. Interestingly, several of the tumours stud- ied have additional translocations involving other onco- genes, suggesting that c-ref mutations are but one step in a process of Rel-induced leukaemogenesis.

Structure of the leucine zipper by Tom Alber

O’SHEA EK, KLEMM JD, KIM PS, ALBER T: X-ray Struc- ture of the GCN4 Leucine Zipper, a Two-stranded, ParaIIel Coiled Coil. Science l%l, 254~539-544.

The first high resolution X-ray cfystal structure of a leucine zipper. The diagrams in this work illustrate im- portant structural features.

O’SHEA EK, RUTKOWSKI R, KIM PS: Mechanism of Speci- ficity in the Fos-Jun Oncoprotein Dimer. Cell 192, 68:699-708.

Extensive physical analysis of hybrid leucine-zipper pep- tides shows that electrostatic complementarity stabi- lizes the Fos-Jun heterodimer and anti-complementarity destabilizes the Fos homodimer.

Volume 2 Number 5 1992

Mechanisms of liver-specific gene expression by Frances M. Sladek and James E. Darnell

CHRISTY RJ, KAESTNER KH, GEIMAN DE, LANE MD: CCAAT/Enhancer Binding Protein Gene Promoter: Binding of Nuclear Factors During Differentiation of 3T3-Ll Pre-adipocytes. Proc Nat1 Acad Sci LISA 1991, 88:2593-2597.

The first work analyzing the promoter of a liver-enriched transcription factor. The authors lind that C/EBPy is regu- lated not only by a factor present in undifferentiated cells (preadipocytes) but also by a C/EBP-like factor. This re- sult suggests the occurrence of autoregulation.

bbWDEL DB, KHAVARI PA, CONIEY PB, GRAVES MIS, HANSEN IP, ADMON A, CRABTREE GR Characteriza- tion of a Cofactor that Regulates Dimerkation of a Mammalian Homeodomain Protein. Science 1931, 254:1762-1767.

Presents the first evidence indicating that a non-DNA- binding protein (DCoH) might play a role in tissue-re- stricted gene expression. Unlike other such factors (also termed adapters, co-activators or bridging proteins) that have recently been described, this co-factor does not ap- pear to interact with the basal transcription machinery. Rather, it appears to function by stabilizing HNF-101 (and HNF-10) homodimers.

Myb: a transcriptional activator linking proliferation and differentiation in hematopoietic cells by Thomas Graf

MUCENSKI ML, McLm K, KIER AB, SW-ERDLOW SH, SCHREINER CM, MILLER TA, PIETRYGA DW, Scorn, WJ, POITER SS: A Functional c-myb Gene is Required for Normal Murine Fetal Hepatic Hematopoiesis. Cell 1991, 65:6n-689.

In this work, c-m@ is inactivated in embryonic stem cells by homologous recombination, and transgenic mice homozygous for the alteration are obtained by breed- ing. The mice develop a severe anemia at approxi-

265

Page 2: Myb: a transcriptional activator linking proliferation and differentiation in hematopoietic cells

mately day 14, indicating that adult but not embryonic hematopoiesis requires the expression of an intact c- myb gene.

BURK 0, KLEMPNAUER K-H: Estrogen-dependent Al- terations in Differentiation State of Myeloid Cells Caused by a v-my&estrogen Receptor Fusion Pro- tein. EAfBO J 1991, 10:3713-3719. Demonstrates that the transfection of a chimera incorpo- rating sequences encoding both v-Myb and the estrogen receptor, into a v- myc transformed chick macrophage cell line, induces a partial retrodiiferentiation. This effect is dependent on the addition of estrogen. Furthermore, a novel gene that is indirectly regulated by v-myb is identi- fied.

OPPENHEIMER DG, HERMAN PL, SIVAKUMARAN S, ESCH J, MARKS MD: A myb Gene Required for Leaf T&home Differentiation in Arabidopsis is Expressed in Stip- ules. Cell 1991, 67483-493. This work shows that in the crucifer, Arab*& tbali- anu, expression of a my&elated gene, GL-1, is re- quired for the initiation of differentiation of hair cells (tri- chomes). This gene is a member of the extended myb family in Arabidcqsis

The Drosophila nuclear receptors: new insight into the actions of nuclear receptors in development by Anthony E. Oro, Michael McKeown and Ronald M. Evans

KOELLE MR, TALBOT WS, SEGRAVES WA, BENDER MT, CHERBAS P, Hocmss DS: The Drosophila EcR Gene Encodes an Ecdysone Receptor, a New Member of the Steroid Receptor Superfamily. a& 1991, 67359-77. Describes the identilication of a receptor for ecdysone. The authors show that this protein is the major ecdysone receptor gene in the Drosophila genome but that other EcR immunoreactive proteins exist.

STEINGRIMSSON E, PIGNONI F, IL&W G, AND LENGYEL J: Dual Role of the Drosophila Pattern Gene tallless in Embryonic Termini. Science 1991, 254:418-421. Demonstrates that when tailless is expressed ectopically, tailless is active and causes pattern deletions by altering the expression of gap genes like Kruppel and knilps.

Activation of HIV transcription by Tat by Alan D. Frankel

WEEKS KM, CROTHERS DM: RNA Recognition by Tat- derived Peptides: Interaction in the Major Groove? Cell 1991, 66:577-588. This study identifies nucleotides in TAR that are essential for Tat-peptide binding and the authors propose a model for specific RNA recognition in which there is increased accessibility to bases in the major groove near bulges.

MARCINW RA, SHARP PA HIV-1 Tat Protein Promotes Formation of More-processive Elongation Complexes. EMBO J 1991, 10:41894196.

This study determines quantitative parameters of Tat transactivation in vitro and concludes that there are two classes of elongation complexes, a ‘less-processive’ and a ‘more-processive’ form, with Tat promoting the forma- tion of ‘more-processive’ complexes.

SOUTHGATE CD, GREEN MR: The HIV-l Tat Protein Ac- tivates Transcription from an Upstream DNA-binding Site: Implications for Tat Function. Genes Dev 1931, 5:24962507.

Tat-GAL4 fusions are shown to activate transcription from upstream GAL4 DNA-binding sites, suggesting that Tat may activate transcription through a mechanism com- mon to other transcriptional activators.

Expression of spatially regulated genes in the sea urchin einbryo by James A. Coffman and Eric H. Davidson

GRADE JE, GAGNON ML, YING Y, ANGERER RC, ANGERER LM: Expression of Two mRNAs Encod- ing EGF-related Proteins Identifies Subregions of Sea Urchin Embryonic Ectoderm. Dev Biol 1991, 143:44-57.

The authors use in situ hybridization to delineate the expression patterns of two different EGF-related genes, SpEGFIand SpEGFII% While the two genes are expressed in the same regions of the oral and aboral ectoderm, later in development (i.e. by pluteus stage) the expression of SpEGFIZ becomes confined to speciIic subsets of cells within these regions. Interestingly, one of these subsets of cells (that located at the vertex of the aboral ectoderm) is the same as that to which the expression of the home- odomain gene, SpHboxl, becomes conlined.

VENUTI JM, GOLDBERG L, C -oR’rY T, OLSON EN, KLEIN WH: A Myogenic Factor from Sea Urchin Em- bryos Capable of Programming Muscle Diierentia- tion in Mammalian Cells. Proc Nat1 Acad Sci USA 1991, 88:6219-6223.

The authors use a cDNA corresponding to the basic helix-loop-helix domain of mouse myogenin to obtain the cDNA encoding the sea urchin myogenic factor, SUM-l. Recombinant SUM-l is shown by application of the gelshift technique to interact with the xE-2 site in the muscle creatine kinase enhancer, and to activate a muscle-specific program of differentiation when trans- fected into lOT1/2 cells. The pattern of expression of SUM-1 in sea urchin embryos is shown by immunological methods to be restricted to muscle precursors, consistent with the gene being involved in muscle differentiation in these embryos.

266 @ 1992 Current Biology