Mechanistic Insights into HP1α CSD Oligomerization and the Role of Motif-Containing Proteins.

HP1 oligomerization is crucial for chromatin compaction, transcriptional regulation, and heterochromatin maintenance. The dynamic transition between HP1 monomeric, dimeric, and higher-order oligomeric states modulates the chromatin structure and phase separation. By controlling the HP1 oligomerization dynamics, chromatin-associated processes involving HP1 can be regulated.

The HP1 box of KAP1 organizes HP1α for silencing of endogenous retroviral elements in embryonic stem cells.

Repression of endogenous retroviral elements (ERVs) is facilitated by KAP1 (KRAB-associated protein 1)-containing complexes, however the underlying mechanism remains unclear. Here, we show that binding of KAP1 to the major component of the heterochromatin spreading and maintenance network, HP1α, plays a critical role in silencing of repetitive elements. Structural, biochemical and mutagenesis studies demonstrate that the association of the HP1 box of KAP1 (KAP1) with the chromoshadow domain of HP1α (HP1α) leads to a symmetrical arrangement of HP1α and multimerization that may promote the closed state of chromatin.

Transcriptome analysis of Huh7 cells upon Chikungunya virus infection and capsid transfection reveals regulation of distinct cellular and metabolic pathways.

Chikungunya virus (CHIKV) causes persistent arthritis and neurological problems imposing a huge burden globally. The present study aims to understand the interaction mechanism of Chikungunya virus and CHIKV-capsid in Huh7 cells. The RNA-sequencing and qRT-PCR method was used for the transcript and gene profiles of CHIKV virus and CHIKV capsid alone.

Molecular basis for nuclear accumulation and targeting of the inhibitor of apoptosis BIRC2.

The inhibitor of apoptosis protein BIRC2 regulates fundamental cell death and survival signaling pathways. Here we show that BIRC2 accumulates in the nucleus via binding of its second and third BIR domains, BIRC2 and BIRC2, to the histone H3 tail and report the structure of the BIRC2-H3 complex. RNA-seq analysis reveals that the genes involved in interferon and defense response signaling and cell-cycle regulation are most affected by depletion of BIRC2.

Non-histone binding functions of PHD fingers.

Plant homeodomain (PHD) fingers comprise a large and well-established family of epigenetic readers that recognize histone H3. A typical PHD finger binds to the unmodified or methylated amino-terminal tail of H3. This interaction is highly specific and can be regulated by post-translational modifications (PTMs) in H3 and other domains present in the protein.

Role of nuclear localization signals in the DNA delivery function of Chikungunya virus capsid protein.

Capsids of several RNA viruses are reported to have unconventional roles attributed to their subcellular trafficking property. The capsid of CHIKV is also found to localize in the nucleus, but the rationale is not yet clear. To understand the role of the nuclear-localized capsid, we examined the nucleic acid binding and cargo delivery activity of the CHIKV capsid.

Evaluation of novobiocin and telmisartan for anti-CHIKV activity.

Chikungunya has re-emerged as an epidemic with global distribution and high morbidity, necessitating the need for effective therapeutics. We utilized already approved drugs with a good safety profile used in other diseases for their new property of anti-chikungunya activity. It provides a base for a fast and efficient approach to bring a novel therapy from bench to bedside by the process of drug-repositioning.

In-silico and biophysical investigation of biomolecular interaction between naringin and nsP2 of the chikungunya virus.

Chikungunya virus; the pathogen for chikungunya febrile and arthritic disease, having 11.8 kb positive-sense RNA genome encodes polyproteins for structural and non-structural regions. The polyprotein (P1234) corresponding to the non-structural part from 5' end gets auto-cleaved by the action of nsP2 protease, which leads to the generation of individual functional enzymatic proteins like nsP4, nsP1, nsP2 and nsP3.