#NEET MCQ

Eukaryotic chromatin and chromosome

SWI/SNF complex is involved in:

Chromatin structure generally impedes transcription factor binding, requiring active remodeling. ATP-dependent remodeling complexes utilize energy from ATP hydrolysis to slide, evict or restructure nucleosomes exposing DNA. SWI/SNF family, containing BRG1 or BRM ATPase, disrupts histone-DNA contacts creating nucleosome-depleted regions at enhancers and promoters, essential for inducible transcription activation and DNA repair. Mutations in SWI/SNF subunits drive rhabdoid tumors and other cancers. It cooperates with histone acetylation opening chromatin, contrasting with ISWI and CHD families spacing nucleosomes regularly. SWI/SNF governs accessibility rather than histone synthesis.

Ref: Clapier et al., Nat Rev Mol Cell Biol 2017; Alberts et al., Chapter 4: SWI/SNF Complex Chromatin Remodeling

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Eukaryotic chromatin and chromosome

Polycomb proteins cause:

Polycomb group proteins maintain developmental regulators silenced through epigenetic memory. PRC2 complex containing EZH2, EED, SUZ12 catalyzes H3K27 trimethylation, PRC1 containing BMI1, RING1B ubiquitinates histone H2A at lysine 119 and compacts chromatin, blocking SWI/SNF remodeling and preventing RNA polymerase II elongation. Targets include HOX clusters and lineage transcription factors. Compaction renders chromatin inaccessible. Polycomb loss results in ectopic gene activation and homeotic transformations. Unlike constitutive activators, Polycomb establishes facultative heterochromatin reversible during differentiation and reprogramming processes, ensuring cell identity maintenance.

Ref: Lewis Polycomb 1978; Lodish et al., Molecular Cell Biology, Chapter 8: Polycomb Proteins Cause Gene Repression

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Eukaryotic chromatin and chromosome

Which histone modification activates transcription?

Active promoter epigenetic signature includes specific histone methylation. H3 lysine 4 trimethylation deposited by SET1 and MLL complexes at transcription start sites recruits chromatin remodelers, histone acetyltransferases and general transcription factor TFIID via TAF3 PHD finger recognition, reducing nucleosome stability and stimulating preinitiation complex assembly and pause release. Conversely H3K9 trimethylation and H3K27 trimethylation deposited by SUV39H and Polycomb EZH2 cause repression. H4K20 trimethylation marks pericentric heterochromatin. Thus H3K4 trimethylation functions as universal epigenetic hallmark of actively transcribed euchromatic genes across eukaryotes.

Ref: Santos-Rosa et al., Nature 2002; Alberts et al., Molecular Biology of the Cell, Chapter 4: H3K4me3 Active Transcription

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Eukaryotic chromatin and chromosome

H3K9 methylation marks:

Histone code marks specific chromatin states. H3 lysine 9 di and trimethylation catalyzed by SUV39H1 and SUV39H2 methyltransferases creates high affinity binding site for heterochromatin protein 1 alpha via its chromodomain, inducing spreading, compaction and transcriptional repression. H3K9 trimethylation enriched at pericentric satellite repeats, subtelomeric repeats and retrotransposons characterizes constitutive heterochromatin, contrasting with H3K4 trimethylation at active promoters. HP1 oligomerization and interaction with DNMTs maintain domain stability. Disruption causes position effect variegation, ectopic transcription and chromosome missegregation defects compromising genome stability severely.

Ref: Bannister et al., Nature 2001; Lodish et al., Molecular Cell Biology, 9th ed., Chapter 8: H3K9 Methylation Heterochromatin Mark

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Eukaryotic chromatin and chromosome

Histone tails are site of:

Histone octamer contains flexible unstructured N-terminal tails and protruding C-termini extending beyond DNA gyres. These lysine, arginine and serine rich segments undergo extensive covalent post-translational modifications including acetylation, methylation, phosphorylation, ubiquitination and sumoylation catalyzed by writer enzymes and erased by erasers. Modifications alter electrostatic charge and create binding sites for effector proteins containing bromodomains, chromodomains and PHD fingers, forming combinatorial histone code that governs accessibility, transcription activation, repression, replication timing and DNA repair without altering fundamental histone DNA wrapping structure.

Ref: Strahl and Allis 2000 Histone Code Hypothesis; Alberts et al., Chapter 4: Histone Tails Site of Modifications

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Eukaryotic chromatin and chromosome

Kinetochore assembles at:

Kinetochore is large multiprotein structure assembling exclusively at centromeric chromatin containing CENP-A nucleosomes. During mitosis inner kinetochore components CENP-C, CENP-T, CENP-I constitutively associate with centromere, outer KMN network including Ndc80, Mis12, KNL1 complexes binds plus ends of spindle microtubules. This linkage transmits pulling forces to separate sister chromatids and activates spindle assembly checkpoint via Mad2, BubR1 until biorientation achieved. Telomeres cap ends, replication origins fire throughout genome, NORs build nucleolus, whereas kinetochore location solely defines segregation platform at centromere region.

Ref: Cheeseman and Desai 2008 Nat Rev Mol Cell Biol; Lodish et al., Chapter 19: Kinetochore Assembles at Centromere

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