Regulatory architecture of housekeeping genes is driven by promoter assemblies.

TitleRegulatory architecture of housekeeping genes is driven by promoter assemblies.
Publication TypeJournal Article
Year of Publication2023
AuthorsDejosez M, Dall'Agnese A, Ramamoorthy M, Platt J, Yin X, Hogan M, Brosh R, Weintraub AS, Hnisz D, Abraham BJ, Young RA, Zwaka TP
JournalCell Rep
Volume42
Issue5
Pagination112505
Date Published2023 May 30
ISSN2211-1247
KeywordsEnhancer Elements, Genetic, Genes, Essential, Promoter Regions, Genetic, Transcription Factors
Abstract

Genes that are key to cell identity are generally regulated by cell-type-specific enhancer elements bound by transcription factors, some of which facilitate looping to distant gene promoters. In contrast, genes that encode housekeeping functions, whose regulation is essential for normal cell metabolism and growth, generally lack interactions with distal enhancers. We find that Ronin (Thap11) assembles multiple promoters of housekeeping and metabolic genes to regulate gene expression. This behavior is analogous to how enhancers are brought together with promoters to regulate cell identity genes. Thus, Ronin-dependent promoter assemblies provide a mechanism to explain why housekeeping genes can forgo distal enhancer elements and why Ronin is important for cellular metabolism and growth control. We propose that clustering of regulatory elements is a mechanism common to cell identity and housekeeping genes but is accomplished by different factors binding distinct control elements to establish enhancer-promoter or promoter-promoter interactions, respectively.

DOI10.1016/j.celrep.2023.112505
Alternate JournalCell Rep
PubMed ID37182209
PubMed Central IDPMC10329844
Grant ListR01 GM129329 / GM / NIGMS NIH HHS / United States
R01 HD100518 / HD / NICHD NIH HHS / United States
P01 GM081627 / GM / NIGMS NIH HHS / United States
R35 GM144283 / GM / NIGMS NIH HHS / United States
S10 OD028520 / OD / NIH HHS / United States