Specific Organization of the Negative Response Elements for Retinoic Acid and Thyroid Hormone Receptors in Keratin Gene Family
Year: 1997
Type: article
Abstract: Retinoic acid and thyroid hormone are im.portantregulators of epidermal growth, differentiation, and hotneostasis.Retinoic acid is extensively used in the treatment of many epidennal disorders ranging from wrinkles to skin cancers.Retinoic acid and thyroid hormone directly control the transcription of differentiation-specific genes including keratins.Their effect is mediated through nuclear receptors RARand T3R.We have previously identified the response element in the K14 gene, K14RARE/TRE, to which these receptors bind, and found that it consists of a cluster of five half-sites with variable spacing and orientation.To deternune whether this specific structure is found in other keratin genes, we have mapped and analyzed the RARE/TRE elements in three additional epidermal keratin genes: KS, K6, and K17.We used three different approaches to identifY these elements: co-transfection of T hyro id ho rm o ne (T 3), stero ids, and ac ti ve m etabo li tes of vitamins A and IJ 3 b elo ng to a brge gro up of factors that co ntribute to ve rtebrate d evelo pm ent and ho m eos tasis.Th ey serve as biologic signal s that co ntro l cell grow th and differen tiatio n.Th ese ho rmo n es and vitam in s m ed iate thei r eiJec ts throu gh nucl ear rece pto rs, transcrip tio n fa cto rs that directl y regubte ge ne tran scri ptio n .Nu clear recepto rs ha ve seve ral fun ction s.Th ey bin d spec ifi c li gand , th ey recogni ze and bind DNA sequ en ces in the targe t genes, and th ey eith er stimulate or inhibi t express io n of pa rti cul ar gen es (Man ge lsdo rf er nl, 1995).T he spec ifi c DNA sequ en ces are ca lled response eleme nts (R E).Natura ll y occ urrin g REs co ntai n hexa m er sites ho m o logo us to the co nse nsus pa lind ro 111 e AGGT C A, design ated '1s a "core site " or " half-site" (Um eso no cl nl, . 1 99 1; Perlm an cl nl, 1993) .Spa cin g and o ri entati o n between th e half- sites determin es th e spec ifi city of particular nucl ea r rcct:pto r b in din g (Um eso no er nl, 199 '1; N aa r er a/, 1991 ).AJth o ugh no t co mpl e tely Man uscri pt rece ived March 26, I \>97; revised June ' .1,I 997; accepted for publi cation Jun e I t'i, 19\>7.
Institutions: NYU Langone Health, New York University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,800
OpenAlex ID: W1987128150