
@article {91470,
	title = {An interdependent network of functional enhancers regulates transcription and EZH2 loading at the INK4a/ARF locus.},
	journal = {Cell Rep},
	volume = {34},
	year = {2021},
	month = {2021 Mar 23},
	pages = {108898},
	abstract = {<p>The INK4a/ARF locus encodes important cell-cycle regulators p14, p15, and p16. The neighboring gene desert to this locus is the most reproducible GWAS hotspot that harbors one of the densest enhancer clusters in the genome. However, how multiple enhancers that overlap with GWAS variants regulate the INK4a/ARF locus is unknown, which is an important step in linking genetic variation with associated diseases. Here, we show that INK4a/ARF promoters interact with a subset of enhancers in the cluster, independent of their H3K27ac and eRNA levels. Interacting enhancers transcriptionally control each other and INK4a/ARF promoters over long distances as an interdependent single unit. The deletion of even a single interacting enhancer results in an unexpected collapse of the entire enhancer cluster and leads to EZH2 enrichment on promoters in an ANRIL-independent manner. Dysregulated genes genome-wide mimic 9p21-associated diseases under these scenarios. Our results highlight intricate dependencies of promoter-interacting enhancers on each other.</p>
},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2021.108898},
	author = {Farooq, Umer and Saravanan, Bharath and Islam, Zubairul and Walavalkar, Kaivalya and Singh, Anurag Kumar and Jayani, Ranveer Singh and Meel, Sweety and Swaminathan, Sudha and Notani, Dimple}
}
@article {94543,
	title = {IP3-mediated Ca2+ signals regulate larval to pupal transition under nutrient stress through the H3K36 methyltransferase Set2.},
	journal = {Development},
	volume = {148},
	year = {2021},
	month = {2021 Jun 01},
	abstract = {<p>Persistent loss of dietary protein usually signals a shutdown of key metabolic pathways. In Drosophila larvae that have reached a {\textquoteright}critical weight{\textquoteright} and can pupariate to form viable adults, such a metabolic shutdown would needlessly lead to death. Inositol 1,4,5-trisphosphate-mediated calcium (IP3/Ca2+) release in some interneurons (vGlutVGN6341) allows Drosophila larvae to pupariate on a protein-deficient diet by partially circumventing this shutdown through upregulation of neuropeptide signaling and the expression of ecdysone synthesis genes. Here, we show that IP3/Ca2+ signals in vGlutVGN6341 neurons drive expression of Set2, a gene encoding Drosophila Histone 3 Lysine 36 methyltransferase. Furthermore, Set2 expression is required for larvae to pupariate in the absence of dietary protein. IP3/Ca2+ signal-driven Set2 expression upregulates key Ca2+-signaling genes through a novel positive-feedback loop. Transcriptomic studies, coupled with analysis of existing ChIP-seq datasets, identified genes from larval and pupal stages that normally exhibit robust H3K36 trimethyl marks on their gene bodies and concomitantly undergo stronger downregulation by knockdown of either the intracellular Ca2+ release channel IP3R or Set2. IP3/Ca2+ signals thus regulate gene expression through Set2-mediated H3K36 marks on select neuronal genes for the larval to pupal transition.</p>
},
	issn = {1477-9129},
	doi = {10.1242/dev.199018},
	author = {Mitra, Rishav and Richhariya, Shlesha and Jayakumar, Siddharth and Notani, Dimple and Hasan, Gaiti}
}
