
@article {159721,
	title = {upstream deletion leads to dysregulation of  and autosomal gene expression.},
	journal = {Genome Res},
	year = {2025},
	month = {2025 Aug 06},
	abstract = {<p>long noncoding RNA is the master regulator of the X-Chromosome inactivation (XCI) process. is expressed from the inactive X and coats the inactive X to facilitate XCI. -regulation of expression remains poorly understood in the context of maintenance of XCI. Here, we have explored the role of the upstream sequences (\~{}6 kb) lying between and in the regulation of and XCI in mouse extra-embryonic endoderm stem cells (XEN), which represent the maintenance phase of imprinted XCI. Here, we show that the deletion of this upstream sequence in the inactive X leads to the upregulation of expression accompanied by the dispersal of the cloud. Notably, we find the loss of enrichment of repressive marks such as H3K27me3, H4K20me1, and MacroH2A, except that of H2AK119ub, in dispersed nuclei. However, X-linked genes remain silent despite dispersal and loss of enrichment of repressive marks. Notably, we find that many autosomal genes, including cohesin , are dysregulated in -upstream-deleted cells. Additionally, we demonstrate that -upstream deletion leads to alterations of topological contacts of the locus with its upstream positive regulator and across the inactive X and autosomes. Finally, we show genome-wide alterations of the occupancy of architectural proteins CTCF/RAD21, including at many loci of the inactive X such as the upstream regions and the locus, which is critical for maintaining inactive X conformation. Taken together, we demonstrate that the upstream sequence imparts a multifaceted role in genome regulation beyond the XCI.</p>
},
	issn = {1549-5469},
	doi = {10.1101/gr.279822.124},
	author = {Majumdar, Sudeshna and Bammidi, Lakshmi Sowjanya and Naik, Hemant C and Manhas, Avinchal and Baro, Runumi and Kalita, Akash and Naskar, Amlan Jyoti and Nidharshan, Sundarraj and Bariha, Girija S and Notani, Dimple and Gayen, Srimonta}
}
@article {71098,
	title = {Ligand dependent gene regulation by transient ERα clustered enhancers.},
	journal = {PLoS Genet},
	volume = {16},
	year = {2020},
	month = {2020 Jan 06},
	pages = {e1008516},
	abstract = {<p>Unliganded Estrogen receptor alpha (ERα) has been implicated in ligand-dependent gene regulation. Upon ligand exposure, ERα binds to several EREs relatively proximal to the pre-marked, or persistent, ERα-bound sites and affects transient but robust gene expression. However, the underlying mechanisms are not fully understood. Here we demonstrate that upon ligand stimulation, persistent sites interact extensively, via chromatin looping, with the proximal transiently ERα-bound sites, forming Ligand Dependent ERα Enhancer Cluster in 3D (LDEC). The E2-target genes are regulated by these clustered enhancers but not by the H3K27Ac super-enhancers. Further, CRISPR-based deletion of TFF1 persistent site disrupts the formation of its LDEC resulting in the loss of E2-dependent expression of TFF1 and its neighboring genes within the same TAD. The LDEC overlap with nuclear ERα condensates that coalesce in a ligand and persistent site dependent manner. Furthermore, formation of clustered enhancers, as well as condensates, coincide with the active phase of signaling and their later disappearance results in the loss of gene expression even though persistent sites remain bound by ERα. Our results establish, at TFF1 and NRIP1 locus, a direct link between ERα condensates, ERα enhancer clusters, and transient, but robust, gene expression in a ligand-dependent fashion.</p>
},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1008516},
	author = {Saravanan, Bharath and Soota, Deepanshu and Islam, Zubairul and Majumdar, Sudeshna and Mann, Rajat and Meel, Sweety and Farooq, Umer and Walavalkar, Kaivalya and Gayen, Srimonta and Singh, Anurag Kumar and Hannenhalli, Sridhar and Notani, Dimple}
}
