Biology subjects

Umer, Z.

Publications and source records attributed to Umer, Z..

3 recordsLinked to original sources

bioRxiv2021

Interplay between BALL and CBP maintains H3K27 acetylation on active genes in Drosophila

CREB binding protein (CBP) is a multifunctional transcriptional co-activator that interacts with a variety of transcription factors and acts as a histone acetyltransferase. In Drosophila, CBP mediated acetylation of histone H3 lysine 27 (H3K27ac) is a known hallmark of gene activation regulated by trithorax group proteins (trxG). Recently, we have shown that a histone kinase Ballchen (BALL) substantially co-localizes with H3K27ac at trxG target loci and is required to maintain gene activation in Drosophila. Here, we report direct interaction between BALL and CBP, which positively regulates H3K27ac. Analysis of genome-wide binding profile of BALL and CBP reveals major overlap and their co-localization at actively transcribed genes. We show that BALL biochemically interacts with CBP and depletion of BALL results in drastic reduction in H3K27ac. Together, these results demonstrate a previously unknown synergy between BALL and CBP and reveals a potentially new pathway required to maintain gene activation during development.

genomics↗

bioRxiv2021

Polycomb requires Tcp-1η chaperonin for maintaining gene silencing in Drosophila

In metazoans, heritable states of cell type specific gene expression patterns linked with specialization of various cell types constitute transcriptional cellular memory. Evolutionarily conserved Polycomb group (PcG) and trithorax group (trxG) proteins contribute to the transcriptional cellular memory by maintaining heritable patterns of repressed and active expression states, respectively. Although chromatin structure and modifications appear to play a fundamental role in maintenance of repression by PcG, the precise targeting mechanism and the specificity factors that bind PcG complexes to a defined region in chromosomes remain elusive. Here we report a serendipitous discovery that uncovers a direct molecular interaction between Polycomb (PC) and TCP-1 Ring Complex (TRiC) chaperonin subunit, Tcp-1{eta} in Drosophila. Tcp-1{eta} interacts with PC at chromatin to maintain repressed states of homeotic and non-homeotic targets of PcG, which supports a strong genetic interaction observed between Pc and Tcp-1{eta} mutants. Depletion of Tcp-1{eta} results in dissociation of PC from chromatin and redistribution of an abundant amount of PC in cytoplasm. We propose that Tcp-1{eta} is an important modulator of PC, which helps PC recruitment at chromatin and compromising Tcp-1{eta} can directly influence an evolutionary highly conserved epigenetic network that supervises the appropriate cellular identities during development and homoeostasis of an organism. Significance StatementSilencing of key developmental genes, e.g, Hox genes, by PcG is a hallmark of differential gene expression patterns associated with cell fate determination. Here we describe a previously unknown molecular and genetic interaction of Polycomb (PC) with Tcp-1{eta} subunit of TRiC chaperonin complex in Drosophila. Compromising Tcp-1{eta} function results in de-repression of PcG targets and a concomitant loss of PC from chromatin. Moreover, depletion of Tcp-1{eta} leads to redistribution of PC in cytoplasm. Molecular interaction of PC with Tcp-1{eta} highlights a novel factor which helps PC recruitment at chromatin. We propose that Tcp-1{eta} chaperonin is one of the specificity factors and part of the targeting mechanism that binds PC to specific regions on chromosomes.

genetics↗

bioRxiv2020

Kinome-wide RNAi screen uncovers role of Ballchen in maintenance of gene activation by trithorax group in Drosophila

Polycomb group (PcG) and trithorax group (trxG) proteins are evolutionary conserved factors that contribute to cell fate determination and maintenance of cellular identities during development of multicellular organisms. The PcG behaves as repressors to maintain heritable patterns of gene silencing and trxG act as anti-silencing factors by maintaining activation of cell type specific genes. Genetic and molecular analysis has revealed extensive details about how different PcG and trxG complexes antagonize each other to maintain cell fates, however the cellular signaling components that contribute to maintenance of gene expression by PcG/trxG remain elusive. Here, we report an ex vivo kinome-wide RNAi screen in Drosophila aimed to identify cell signaling genes that facilitate trxG to counteract PcG mediated repression. From the list of trxG candidates, Ballchen (BALL), a histone kinase, known to phosphorylate histone H2A at threonine 119 (H2AT119p), was characterized as a trxG regulator. The ball mutant exhibit strong genetic interaction with Polycomb (Pc) and trithorax (trx) mutants and loss of BALL also affects expressions of trxG target genes in ball mutant embryos. BALL co-localizes with Trithorax on chromatin and depletion of BALL results in increased H2AK118 ubiquitination, a histone mark central to PcG mediated gene silencing. Moreover, analysis of genome-wide binding profile of BALL shows an overlap with 85% known binding sites of TRX across the genome. Both BALL and TRX are highly enriched at actively transcribed genes, which also correlate with presence of H3K4me3 and H3K27ac. We propose that BALL mediated signal positively contributes to the maintenance of gene activation by trxG by counteracting the repressive effect of PcG.

molecular biology↗