(Geyer et al. 1988b; Peifer and Bender 1988;Flavell et al. 1990;Smith and Corces 1992). This effect has been studied in detail in the case of a gypsy-induced mu- Cold Spring Harbor Laboratory Press on May 9, 2018 -Published by genesdev.cshlp.org Downloaded from

Mutations in the suppressor of Hairy‐wing [su(Hw)] locus reverse the phenotype of a number of tissue‐specific mutations caused by insertion of a gypsy retrotransposon. The su(Hw) gene encodes a zinc finger protein which binds to a 430 bp region of gypsy shown to be both necessary and sufficient for its mutagenic effects. su(Hw) protein causes mutations by inactivation of enhancer elements only when a su(Hw) binding region is located between these regulatory sequences and a promoter. To understand the molecular basis of enhancer inactivation, we tested the effects of su(Hw) protein on expression of the mini‐white gene. We find that su(Hw) protein stabilizes mini‐white gene expression from chromosomal position‐effects in euchromatic locations by inactivating negative and positive regulatory elements present in flanking DNA. Furthermore, the su(Hw) protein partially protects transposon insertions from the negative effects of heterochromatin. To explain our current results, we propose that su(Hw) protein alters the organization of chromatin by creating a new boundary in a pre‐existing domain of higher order chromatin structure. This separates enhancers and silencers distal to the su(Hw) binding region into an independent unit of gene activity, thereby causing their inactivation.

5eparate re9u1at0ry e1ement5 are re5p0n5161e f0r the c0mp1ex pattern 0f t155ue-5pec1f1c and deve10pmenta1 tran5cr1pt10n 0f the ye110w f0cu5 1n Dr050ph11a me1an09a5ter Pame1a K. 6eyer and V1ct0r 6. C0rce5Department 0f 810109y, 7he J0hn5 H0pk1n5 Un1ver51ty, 8a1t1m0re, Mary1and 21218 U5A DNA 5e4uence5 1nv01ved 1n the c0ntr01 0f the deve10pmenta1 and 5pat1a1 expre5510n 0f the ye110w 10cu5 0f Dr050ph11a were 1dent1f1ed 6y phen0typ1c ana1y515 0f 9erm11ne tran5f0rmant5 carrY1n9 var10u5 1n v1tr0 m0d1f1ed ye110w 9ene5. 7w0 re910n5, 10cated 6etween -2873 6p and -1868 6p and 6etween -1868 6p and -700 6p, act a5 t155ue-5pec1f1c enhancer5 wh1ch re5pect1ve1y re9u1ate ye110w tran5cr1pt10n 1n the w1n95 and 60dy 0f the adu1t f11e5. 5e4uence5 51tuated c105er t0 the mRNA cap 51te, 6etween -225 6p and -91 6p fr0m the 5tart 0f tran5cr1pt10n, are re5p0n5161e f0r ye110w expre5510n 1n the dent1c1e 6e1t5 and m0uth part5 dur1n9 1arva1 deve10pment. F1na11y, c010rat10n 0f the adu1t 6r15t1e5 15 re9u1ated 6y 5e4uence5 10cated 1n the 1ntr0n 0f the ye110w 9ene. 7he5e re5u1t5 1nd1cate the ex15tence 0f 5evera1 5eparate DNA e1ement5 re5p0n5161e f0r the d1fferent pattern5 0f temp0ra1 and 5pat1a1 expre5510n 0f the ye110w 10cu5. [Key W0rd5: Dr050ph11a; 9ene re9u1at10n; enhancer e1ement5] Rece1ved Ju1y 14, 1987; rev15ed ver510n accepted 5eptem6er 10, 1987. 7he ye110w (y, 1-0.0) 10cu5 0f Dr050ph11a me1an09a5ter 15 1nv01ved 1n 9enerat1n9 the pattern 0f P19mentat10n 1n 1arva1 and adu1t cut1cu1ar 5tructure5. Mutat10n5 at th15 10cu5 are rece551ve and chan9e n0rma1 c010rat10n fr0m 6r0wn15h-61ack t0 ye110w. 7he ye110w 9ene ha5 6een c10ned (81e55man 1985; Campu2an0 et a1. 1985; Ch1a et a1. 1986; Parkhur5t and C0rce5 1986), and the pr0te1n c0d1n9 re910n ha5 6een ana1y2ed 1n deta11 (Ch1a et a1. 1986; 6eyer et a1. 1986). 7he 5tructura1 pr0pert1e5 0f the ye110w-enc0ded pr0te1n deduced fr0m the DNA 5e-4uence 5u99e5t that 1t 15 5ecreted and p1ay5 a 5tructura1 r01e 1n p19mentat10n, p055161y 6y cr055-11nk1n9 me1an1n dur1n9 cut1cu1ar tann1n9 (6eyer et a1. 1986). 7he ye110w tran5cr1pt10n un1t 15 c0mp05ed 0f tw0 ex0n5 5eparated 6y a 1ar9e 1ntr0n. 7he 9ene 15 tran5cr16ed 1nt0 a 1.9-k6 p01yadeny1ated RNA wh05e expre5510n 15 re9u1ated 1n a deve10pmenta1 and t155ue-5pec1f1c fa5h10n; maj0r peak5 0f RNA accumu1at10n 0ccur dur1n9 the 1ate em6ry0-ear1y 1arva1 and m1d-t0-1ate pupa1 5ta9e5 0f deve10pment (Parkhur5t and C0rce5 1986). 80th the tran5cr1pt10n 5tart 51te and 5p11c1n9 pattern are 1dent1ca1 f0r the 1arva1 and pupa1 mRNA, 1nd1cat1n9 that deve10pmenta1 expre5510n 15 n0t re9u1ated at e1ther 0f the5e 5tep5 0f mRNA pr0duc-t10n (6eyer et a1. 1986). 7w0 c1a55e5 0f ye110w mutant5 have 6een 1dent1f1ed (6reen 1961). 5evera1 ye110w a11e1e5 (type 1) are am0r-ph1c and exh161t mutant expre5510n 1n a11 p19mented 5tructure5, wherea5 the 5ec0nd c1a55 0f a11e1e5 (type 2) 5h0w mutant expre5510n 1n 50me 5tructure5 and part1a11y 0r fu11y w11d-type expre5510n 1n 0ther5. C010rat10n 1n th15 5ec0nd c1a55 15 a11e1e 5pec1f1c, and m0re than 40 cut1cu1ar 5tructure5 have 6een 1dent1f1ed wh0...

The y2 mutation resulted from the insertion of the gypsy element into the X‐linked yellow locus of Drosophila melanogaster. As a consequence of this insertion, transcriptional enhancers that control the expression of the yellow gene in the wings and body cuticle of adult flies are unable to act on the yellow promoter, resulting in a tissue‐specific phenotype characterized by mutant coloration in these structures. Some yellow null alleles (yn) are able to complement the y2 phenotype giving rise to near wild type y2/yn females. The molecular structure of the yellow locus in complementing and noncomplementing mutations was determined by cloning and sequencing the various alleles examined. From the information obtained in these studies, we propose a model suggesting that the complementing wild type phenotype of y2/yn flies might be due to the ability of functional wing and body cuticle transcriptional enhancers located in the yn locus to act in trans on the promoter of the yellow gene found in the y2‐containing chromosome. Furthermore, this transactivation is abolished by the presence of an intact promoter in cis, suggesting that promoter competition between the yellow genes located on each homolog precludes the activation in trans by transcriptional enhancers in favour of cis effects on their own promoter.

Proteins resident in the inner nuclear membrane and underlying nuclear lamina form a network that regulates nuclear functions. This review highlights a prominent family of nuclear lamina proteins that carries the LAP2-emerin-MAN1-domain (LEM-D). LEM-D proteins share an ability to bind lamins and tether repressive chromatin at the nuclear periphery. The importance of this family is underscored by findings that loss of individual LEM-D proteins causes progressive, tissue-restricted diseases, known as laminopathies. Diverse functions of LEM-D proteins are linked to interactions with unique and overlapping partners including signal transduction effectors, transcription factors and architectural proteins. Recent investigations suggest that LEM-D proteins form hubs within the nuclear lamina that integrate external signals important for tissue homeostasis and maintenance of progenitor cell populations.