Universität zu Köln

Chayengia, Mrinal, Veikkolainen, Ville, Jevtic, Milica and Pyrowolakis, George (2019). Sequence environment of BMP-dependent activating elements controls transcriptional responses to Dpp signaling in Drosophila. Development, 146 (11). CAMBRIDGE: COMPANY BIOLOGISTS LTD. ISSN 1477-9129

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Abstract

Intercellular signaling pathways activate transcription factors, which, along with tissue-specific co-factors, regulate expression of target genes. Responses to TGF beta/BMP signals are mediated by Smad proteins, which form complexes and accumulate in the nucleus to directly bind and regulate enhancers of BMP targets upon signaling. In Drosophila, gene activation by BMP signaling often requires, in addition to direct input by Smads, the signal-dependent removal of the transcriptional repressor Brk. Previous studies on enhancers of BMP-activated genes have defined a BMP-responsive motif, the AE, which integrates activatory and repressive input by the Smad complex and Brk, respectively. Here, we address whether sequence variations within the core AE sequences might endow the motif with additional properties accounting for qualitative and quantitative differences in BMP responses, including tissue specificity of transcriptional activation and differential sensitivity to Smad and Brk inputs. By analyzing and cross-comparing three distinct BMP-responsive enhancers from the genes wit and Dad in two different epithelia, the wing imaginal disc and the follicular epithelium, we demonstrate that differences in the AEs contribute neither to the observed tissue-restriction of BMP responses nor to differences in the utilization of the Smad and Brk branches for transcriptional activation. Rather, our results suggest that the cis-environment of the BMP-response elements not only dictates tissue specificity but also differential sensitivity to the two BMP mediators.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Chayengia, Mrinal UNSPECIFIED UNSPECIFIED UNSPECIFIED Veikkolainen, Ville UNSPECIFIED UNSPECIFIED UNSPECIFIED Jevtic, Milica UNSPECIFIED UNSPECIFIED UNSPECIFIED Pyrowolakis, George UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-146336
DOI:	10.1242/dev.176107
Journal or Publication Title:	Development
Volume:	146
Number:	11
Date:	2019
Publisher:	COMPANY BIOLOGISTS LTD
Place of Publication:	CAMBRIDGE
ISSN:	1477-9129
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language REGULATES SYNAPTIC GROWTH; WISHFUL-THINKING; MORPHOGEN GRADIENT; II RECEPTOR; BRINKER; REPRESSION; TARGET; EXPRESSION; SYNEXPRESSION; MECHANISMS Multiple languages Developmental Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14633