Skip to main content
Pearson+ LogoPearson+ Logo
Ch. 17 - Transcriptional Regulation in Eukaryotes
Klug - Concepts of Genetics 12th Edition
Klug12th EditionConcepts of Genetics ISBN: 9780135564776Not the one you use?Change textbook
All textbooksKlug 12th EditionCh. 17 - Transcriptional Regulation in EukaryotesProblem 30
Chapter 17, Problem 30

Hereditary spherocytosis (HS) is a disorder characterized by sphere-shaped red blood cells, anemia, and other abnormal traits. Ankyrin-1 (ANK1) is a protein that links membrane proteins to the cytoskeleton. Loss of this activity is associated biochemically to HS. However, Gallagher et al. (2010) (J. Clin. Invest. 120:4453–4465) show that HS can also be caused by mutations within a region from -282 to -101 relative to the transcriptional start site, which lead to constitutive transcriptional repression in erythroid cells due to local chromatin condensation. Propose a hypothesis for the function of the -282 to -101 region of the ANK1 gene.

Verified step by step guidance
1
Understand the context: The region from -282 to -101 relative to the transcriptional start site is upstream of the ANK1 gene, indicating it is part of the gene's promoter or regulatory region.
Recall that promoter regions contain specific DNA sequences where transcription factors and other regulatory proteins bind to control gene expression, either activating or repressing transcription.
Given that mutations in this region cause constitutive transcriptional repression and chromatin condensation, hypothesize that this region normally functions as a binding site for transcriptional activators or chromatin remodelers that maintain an open chromatin state to allow ANK1 expression in erythroid cells.
Consider that loss of function mutations here might disrupt binding of these activators or recruit repressors, leading to chromatin condensation and reduced transcription of ANK1, which contributes to the HS phenotype.
Therefore, propose that the -282 to -101 region acts as a positive regulatory element (such as an enhancer or promoter element) necessary for proper transcriptional activation of ANK1 in erythroid cells.

Verified video answer for a similar problem:

This video solution was recommended by our tutors as helpful for the problem above.
Video duration:
1m
Was this helpful?

Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

Gene Promoter and Regulatory Regions

Promoter regions are DNA sequences located upstream of a gene's transcription start site that regulate gene expression. They contain binding sites for transcription factors and other proteins that either activate or repress transcription. The region from -282 to -101 likely functions as a regulatory element influencing ANK1 gene expression in erythroid cells.
Recommended video:
Guided course
09:09
Mapping Genes

Chromatin Structure and Transcriptional Regulation

Chromatin condensation affects gene accessibility by controlling how tightly DNA is packed. When chromatin is condensed, transcription factors cannot access DNA, leading to transcriptional repression. Mutations causing local chromatin condensation in the ANK1 regulatory region can reduce gene expression, contributing to hereditary spherocytosis.
Recommended video:
Guided course
04:35
Chromatin

Role of Ankyrin-1 in Red Blood Cells and Disease Mechanism

Ankyrin-1 links membrane proteins to the cytoskeleton, maintaining red blood cell shape and stability. Loss of Ankyrin-1 function disrupts membrane integrity, causing sphere-shaped cells and anemia in HS. Mutations affecting ANK1 expression or function can thus lead to the disease phenotype.
Recommended video:
Guided course
09:52
Spontaneous Mutations
Related Practice
Textbook Question

During an examination of the genomic sequences surrounding the human β-globin gene, you discover a region of DNA that bears sequence resemblance to the glucocorticoid response element (GRE) of the human metallothionein IIA (hMTIIA) gene. Describe experiments that you would design to test

(1) whether this sequence was necessary for accurate β-globin gene expression and

(2) whether this sequence acted in the same way as the hMTIIA gene's GRE.

532
views
Textbook Question

Marine stickleback fish have pelvic fins with long spines that provide protection from larger predatory fish. Some stickleback fish were trapped in lakes and have adapted to life in a different environment. Many lake populations of stickleback fish lack pelvic fins. Shapiro et al. (2004) (Nature 428:717.723) mapped the mutation associated with the loss of pelvic fins to the Pitx1 locus, a gene expressed in pelvic fins, the pituitary gland, and the jaw. However, the coding sequence of the Pitx1 gene is identical in marine and lake stickleback [Chan et al. (2010). Science 327:5963,302–305]. Moreover, when the Pitx1 coding region is deleted, the fish die with defects in the pituitary gland and the jaw, and they lack pelvic fins. Explain how a mutation near, but outside of, the coding region of Pitx1 may cause a loss of pelvic fins without pleiotropic effects on the pituitary gland and jaw.

623
views
Textbook Question

Although a single activator may bind many enhancers in the genome to control several target genes, in many cases, the enhancers have some sequence conservation but are not all identical. Keeping this in mind, consider the following hypothetical example:

- Undifferentiated cells adopt different fates depending on the concentration of activator protein, Act1.

- A high concentration of Act1 leads to cell fate 1, an intermediate level leads to cell fate 2, and low levels to cell fate 3.

- Research shows that Act1 regulates the expression of three different target genes (A, B, and C) with each having an enhancer recognized by Act1 but a slightly different sequence that alters the affinity of Act1 for the enhancer. Act1 has a high affinity for binding the enhancer for gene A, a low affinity for the gene B enhancer, and an intermediate affinity for the gene C enhancer.

From these data, speculate on how Act1 concentrations can specify different cell fates through these three target genes? Furthermore, which target genes specify which fates?

597
views
Textbook Question

Transcription factors play key roles in the regulation of gene expression, but to do so, they must act within the nucleus. Like most proteins, however, transcription factors are translated in the cytoplasm. To enter the nucleus, transcription factors contain nuclear localization signals, which in some cases can work only when bound to some other molecule such as a steroid hormone. After entering the nucleus, transcription factors must bind to appropriate DNA sites and must interact with other transcription proteins at promoters, enhancers, and silencers. Transcription factors then activate or repress transcription through their activation or repression domains. Many drug therapies target transcription factors. Based on the information provided above, suggest three specific mechanisms through which a successful drug therapy, targeted to a transcription factor, might work.

933
views